The SMG of mice and rats contain a heterologous group of biologically active factors. Some are we... more The SMG of mice and rats contain a heterologous group of biologically active factors. Some are well known, can be obtained at high purity and are well-characterized. There is strong evidence for the presence of others although they have not been purified. Finally, some of them are questionable and/or have not yet been characterized. EPO would be one of the factors whose presence in the SMG is strongly suspected, although its biological activity has not been demonstrated yet. Its presence in the gland, therefore, is only supported by radioimmunoassay data and immunocytochemical methods. Immunoreactive EPO is undetectable in the mouse SMG until the 30th day of postnatal life, increasing thereafter at a uniform rate and reaching adult levels by 50-60 days of age. The parallelism between its concentration in extracts of the gland, the size and relative proportion of GCT cells, could be accepted as indirect evidence for its localization in these cells. The rise in iEPO concentration in SMGs after androgen treatment, its fall following orchiectomy, and its reduction after duct ligation in proportion to the degree of degranulation of GCT cells lend support to the above hypothesis. Salivary secretions induced by either NE or ISO contain high levels of iEPO. A significant depletion of gland content is also observed. These two sets of data indicate that SMG exocrine iEPO secretion occurs and that this secretion is mediated by adrenergic receptors. The question whether the SMG also functions as an endocrine organ in relation to EPO can not be answered at present.
The alpha adrenoceptor that mediates the secretory responses to norepinephrine in submaxillary gl... more The alpha adrenoceptor that mediates the secretory responses to norepinephrine in submaxillary glands was characterized. All three alpha antagonists employed produced in innervated glands parallel displacements of the dose-response curves to norepinephrine, prazosin being 30 and 100 times more potent than phentolamine and yohimbine, respectively. Chronic sympathetic denervation produced supersensitivity to norepinephrine. Under these conditions prazosin also was more potent than yohimbine but the shifts of the dose-response curves to norepinephrine were nonparallel. Potentiation of norepinephrine by cocaine did not modify the effects of prazosin in innervated glands. The nonparallel displacements observed in denervated glands were related to the development of postjunctional supersensitivity of the beta adrenoceptor-mediated responses because after administration of propranolol the displacements produced by prazosin were parallel. Responses to methoxamine were not potentiated by denervation and were competitively antagonized by prazosin in both innervated and denervated glands. Specific [3H]clonidine binding to membranes of submaxillary glands showed at least two independent sites with a KD1 of 0.37 nM and a KD2 of 65 nM. The number of sites of each component was doubled after chronic sympathetic denervation. Binding of [3H]prazosin (KD, 0.43 nM; maximum binding sites, 78.5 fmol/mg of protein) was not affected by denervation. The present findings show that sialagogue responses to sympathomimetic agents are mediated by alpha-1 adrenoceptor activation in both innervated and denervated submaxillary glands. Chronic sympathetic denervation does not produce postjunctional supersensitivity of the alpha-1-mediated responses and the supersensitivity of the beta-mediated responses interferes with determinations of dose-response curves to the sympathetic neurotransmitter.
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright
La obturacion de los conductos radiculares consiste en el relleno permanente del “espacio endodon... more La obturacion de los conductos radiculares consiste en el relleno permanente del “espacio endodontico” y el reemplazo del contenido normalo patologico del conducto por materiales que deben estar bien compactados y adaptados a las paredes del mismo. Al ser imposible la desinfeccion total de los conductos radiculares, es evidente la necesidad de utilizar un sellador endodontico con accion bactericida, o al menos bacteriostatica, que pueda actuar contra las bacterias que persisten luego de la preparacion quirurgica del conducto radicular. El objetivo de este estudio fue evaluar in vitro el poder antiseptico del cemento de Grossman, un material de obturacion muy utilizado en endodoncia, en combinacion con 2 proporciones de yodoformo, sobre bacterias comunmente encontradas en infecciones de origen endodontico. Resultados: el yodoformo puro no evidencio capacidad antiseptica sobre ninguna de las cepas estudiadas. Sin embargo, al asociarse con CG incremento su efecto inhibitorio sobre Stre...
El presente trabajo aporta evidencia de la presencia de receptores de cannabinoides en la glandul... more El presente trabajo aporta evidencia de la presencia de receptores de cannabinoides en la glandula submaxilar de la rata, cuya expresion secircunscribe a componentes acinares y ductales. A su vez, los resultados expuestos confirman la participacion de los receptores de cannabinoides en el control de la secrecion salival, y por ende aportan una explicacion empirica a la hiposialia observada luego del consumo de marihuana (AU) The present study provides evidence for the presence of cannabinoid receptors in rat submandibular gland, whose expression is restricted to acinar and ductal components. In turn, the presented results confirm the involvement of cannabinoid receptors in the control of salivary secretion, and thus provide an empirical explanation to hyposialia observed after marijuana consumption. (AU)
anandamide (6 ! 10-5 M) on salivary secretion. Lipopolysaccharide (5 mg/kg/3 h) injected intraper... more anandamide (6 ! 10-5 M) on salivary secretion. Lipopolysaccharide (5 mg/kg/3 h) injected intraperitoneally and ethanol (3 g/kg/1 h) injected intragastrically inhibited the salivary secretion induced by the sialogogue metacholine; this inhibitory effect was blocked by CB1 and/or CB2 receptor antagonists. Similar to the hypothalamus, these effects seem to be mediated by increased anandamide. In summary, similar mechanisms mediate the inhibitory actions of endocannabinoids and cannabinoids in both hypothalamus and submandibular gland during drug consumption and inflammation.
The aims of the present study were, first, to identify signs of alveolar bone damage in early sta... more The aims of the present study were, first, to identify signs of alveolar bone damage in early stages of experimental periodontitis (EP) and, second, to assess its possible prevention by treatment with cannabinoid receptor 2 agonist HU 308. Experimental periodontitis was induced by injections of lipopolysaccharide (LPS) (1mg/ml) in gums surrounding maxillary and mandibular first molar, 3 days per week, and untreated controls were kept for comparison. Then, a 3-week study was conducted including eighteen new rats (six rats per group): 1) controls; 2) experimental periodontitis rats; and 3) experimental periodontitis rats treated daily with HU 308 (500 ng/ml). After euthanasia, alveolar bone loss was assessed by morphometric and histomorphometric techniques, and the content of prostaglandin E 2 (PGE 2) in gingival tissue was evaluated by radioimmunoassay. The first signs of alveolar bone loss were apparent at 3 weeks of experimental periodontitis (ρ<0.05) in the mandibular first molar, but there was no detectable change at 1 week, leading us to establish 3 weeks as an early stage of experimental periodontitis. Rats subjected to 3-week experimental periodontitis showed less interradicular bone volume, less whole bone perimeter and fewer bone formation areas, and higher periodontal space height, bone resorption areas, number of osteoclasts and gingival content of prostaglandin E 2 than controls, while HU 308 prevented, at least partially, the deleterious effects (ρ<0.001). We can conclude that a 3-week term of lipopolysaccharide-induced periodontitis in rats provides a valid model of the early stage of the disease, as emerging damage is observed in bone tissue. Furthermore, harmful effects at 3 weeks could be prevented by local stimulation of cannabinoid receptor 2, before greater damage is produced.
Objective: Mild and chronic energy restriction results in growth retardation with puberal delay, ... more Objective: Mild and chronic energy restriction results in growth retardation with puberal delay, a nutritional disease known as nutritional dwarfing (ND). The aim of the present study was to assess the profile of hypothalamic luteinizing hormone-releasing hormone (LHRH) release, at baseline and under glutamate stimulation, in ND rats to elucidate gonadotrophic dysfunction. Reproductive ability during refeeding was also studied. Material and methods: At weaning, 60 male rats were assigned to two groups of 30 animals each: a control and an experimental group. Control rats were fed ad libitum with a balanced rodent diet. The experimental group received 80% of the diet consumed by the control group for 4 weeks. After 4 weeks of food restriction, the ND group was fed freely for 8 weeks. Ten rats from each group were sacrificed every 4 weeks for assays. Results: At week 4, body weight and length were significantly diminished in the experimental group vs. the control group (po0.001). No changes were observed in LHRH baseline release, pulse frequency or amplitude in the experimental group compared with the control group at any time. However, under glutamate stimulation, LHRH release was significantly higher in ND rats than in control rats at week 4 (po0.05). Refeeding the ND group allowed the rats to reach overall growth and reproductive ability. Conclusions: The results of the present study suggest that the response to the facilitatory effect of glutamate on LHRH release in post-restricted ND rats is probably related to a lesser central nervous system maturation in relation to their chronological age. The adequate somatic growth and normal reproductive ability attained with refeeding suggest the reversibility of the two energetically costly processes compromised by global, mild and chronic food restriction.
The effects of sub-chronic cadmium (Cd) administration on the structure and subsequent secretory ... more The effects of sub-chronic cadmium (Cd) administration on the structure and subsequent secretory responses of the submaxillary and parotid glands to sialagogues were investigated. Female Wistar rats were injected subcutaneously with cadmium chloride (3.0 mg/kg body weight), 4 times a week for 2, 3 or 4 weeks. Functional and histopathological studies were done 3 days after the last injection, Dose-response curves for norepinephrine and methacholine were obtained. After 2 weeks of Cd administration significant changes in the secretory response to these sialogogues were observed. The dose-response curves after pretreatment with Cd for 3 weeks were also shifted to the right, but the response showed recovery when compared with that of 2-week treated animals. Parotid amylase concentration was also diminished by Cd. Treated rats had reduced acinar diameters, and an increase in acinar cell nuclei per field in both the submaxillary and parotid glands. Thus sub-chronic administration of ionized Cd produces morphological and functional changes in rat salivary glands. Moreover, the extent of tubular and acinar damage matches the degree of gland dysfunction as judged by the diminution of secretory responses to sialagogues
Background: Transient receptor potential vanilloid type-1 (TRPV1) is expressed in oral tissues ce... more Background: Transient receptor potential vanilloid type-1 (TRPV1) is expressed in oral tissues cells and its activity can be regulated by inflammation products and anandamide. The aim of the present study was to evaluate the effects of blocking TRPV1 or specific cannabinoid receptors 1 (CB1r) and 2 (CB2r) on periodontal status of rats subjected to experimental periodontitis (EP). Methods: Male rats were distributed in groups 1) control, 2) lipopolysaccharide induced EP (LPS) and 3) LPS plus capsazepine (Capz, TRPV1 antagonist) application (LPS+Capz). EP was induced by injections of LPS (1 mg/ml) around first molars and treatment was performed with Capz (2 ug/ml) applied locally during six weeks. Additional experiment was performed by applying CB1r and CB2r antagonists (AM251 and AM630) to rats with EP. Results: Capz prevented alveolar bone loss (ABL) on the external crests and in the interradicular bone of the first molars (Periodontal space height: LPS, 270.7±33.5µm versus LPS+Capz, 216.4±19.9µm; ρ<0.01). Inflammatory mediators, like tumor necrosis factor alpha (TNFα) and prostaglandin E 2 (PGE 2), increased by LPS-induced EP, were diminished in gingival tissue of rats treated with Capz. In contrast, application of AM251 and AM630 exacerbated ABL and gingival inflammatory mediators, increased by LPS, altering also biomechanical properties. Conclusions: TRPV1 blockade attenuates periodontal impairment in EP rats, since it reduces local inflammation, unlike CB1r and CB2r blockade. This work lays the foundations for developing This article is protected by copyright. All rights reserved. therapeutics in humans based on the pharmacological manipulation of these receptors to treat periodontal disease.
regulation of submandibular gland secretion in the rat Endothelins participate in the central and... more regulation of submandibular gland secretion in the rat Endothelins participate in the central and peripheral You might find this additional info useful... 40 articles, 10 of which can be accessed free at:This article cites
The aims of the present study were, first, to identify signs of alveolar bone damage in early sta... more The aims of the present study were, first, to identify signs of alveolar bone damage in early stages of experimental periodontitis (EP) and, second, to assess its possible prevention by treatment with cannabinoid receptor 2 agonist HU 308. Experimental periodontitis was induced by injections of lipopolysaccharide (LPS) (1mg/ml) in gums surrounding maxillary and mandibular first molar, 3 days per week, and untreated controls were kept for comparison. Then, a 3-week study was conducted including eighteen new rats (six rats per group): 1) controls; 2) experimental periodontitis rats; and 3) experimental periodontitis rats treated daily with HU 308 (500 ng/ml). After euthanasia, alveolar bone loss was assessed by morphometric and histomorphometric techniques, and the content of prostaglandin E2 (PGE2) in gingival tissue was evaluated by radioimmunoassay. The first signs of alveolar bone loss were apparent at 3 weeks of experimental periodontitis (ρ<0.05) in the mandibular first molar...
American Journal of Physiology-Endocrinology and Metabolism, 2001
Inducible (calcium-independent) nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are imp... more Inducible (calcium-independent) nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are important in the regulation of the function of different organs during infection. A single dose of lipopolysaccharide (LPS; 5 mg/kg ip) within 6 h increased NOS activity (20%) and prostaglandin E (PGE) content (100%) in submandibular glands (SMG) and blocked stimulated salivary secretion in adult male rats. The administration of an iNOS synthesis inhibitor, aminoguanidine (AG), with LPS decreased NOS activity and PGE content. Furthermore, the administration of meloxicam (MLX), an inhibitor of COX-2, blocked the increase in PGE and the production of NO. The incubation of slices of SMG in the presence of 3-morpholinosydnonimine, a donor of NO, increased the release of PGE highly significantly. The incubation of SMG in the presence of a PGE1 analog (alprostadil) increased the production of NO. These results indicate that LPS activates NOS, leading to NO release, which activates COX, generating...
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, Mar 10, 2018
Saliva is very important to oral health, and a salivary deficit has been shown to bring serious p... more Saliva is very important to oral health, and a salivary deficit has been shown to bring serious problems to oral health. There is scant information about the mechanisms through which salivary glands participate in post-tooth extraction socket healing. Therefore, the aim of the present study was to investigate the effect of submandibulectomy (SMx), consisting of the ablation of submandibular and sublingual glands (SMG and SLG, respectively), on PGE signaling and other bone regulatory molecules, such as OPG and RANKL, involved in tooth extraction socket healing. Male Wistar rats, 70 g body weight, were assigned to an experimental (subjected to SMx) or a control group (sham operated). One week later, the animals in both groups underwent bilateral extraction of the first mandibular molars. The effect of SMx on different stages of socket healing after tooth extraction (7, 14, and 30 days) was studied by evaluating some parameters of inflammation, including PGE and its receptors, and of b...
It is known that marijuana use decreases saliva secretion. Therefore, we hypothesized that cannab... more It is known that marijuana use decreases saliva secretion. Therefore, we hypothesized that cannabinoid receptors (CBs) are located in salivary glands to mediate that effect. In these experiments, we used the submandibular gland (SMG) of male rats, which is one of the major salivary glands. Mammalian tissues contain at least two types of CBs, CB1 and CB2, mainly located in the nervous system and peripheral tissues, respectively. Both receptors are coupled to Gi protein and respond by inhibiting the activity of adenylyl cyclase. We demonstrated that both CB1 and CB2 are present in the SMG, each showing specific localizations. The best-known endocannabinoid is anandamide (AEA), which binds with high affinity to CB1 and CB2. We showed that AEA markedly reduced forskolin-induced increase of cAMP content in vitro. This effect was blocked by AM251 and AM630 (CB1 and CB2 antagonists, respectively), indicating that both receptors are implicated in SMG physiology. In addition, we showed that ...
It is known that immune challenge inhibits reproductive function and that endocannabinoids (eCB) ... more It is known that immune challenge inhibits reproductive function and that endocannabinoids (eCB) modulate sexual hormones. However, no studies have been performed to assess whether the endocannabinoid system mediates the inhibition of hormones that control reproduction due to immune system activation during systemic infections. For that reason, we evaluated the participation of the hypothalamic cannabinoid receptor CB1 on hypothalamic-pituitary-gonadal (HPG) axis activity in rats submitted to immune challenge. Male adult rats were treated via intracerebroventricular (i.c.v.) administration with a CB1 antagonist/inverse agonist, (AM251, 500 ng/5 ul), followed by an intraperitoneal (i.p.) injection of lipopolysaccharide (LPS, 5 mg/kg) 15 min later. Plasmatic, hypothalamic and adenohypophyseal pro-inflammatory cytokines, hormones and neuropeptides were assessed 90 or 180 min post-LPS. Plasma concentration of TNFα and adenohypophyseal mRNA expression of Tnfα and Il1β increased 90 and 18...
Se identificó el subtipo alfa1 adrenoceptores como mediador de la respuesta secretoria en la glán... more Se identificó el subtipo alfa1 adrenoceptores como mediador de la respuesta secretoria en la glándula submaxilar de la rata, basándose en el empleo de diferentes dosis de antagonistas adrenérgicos selectivos alfa1 (prazosín), alfa2 (yohimbina) y no selectivo (fenatolamina) ante la acción del neurotransmisor, la noradrenalina. Los parámetros determinados tanto en glándulas normales como crónicamente desnervadas fueron: a) desplazamientos de las curvas dosis-respuesta; b) dosis efectiva 20 microlitros (DE20 ,ul) y c) determinación del pA2. El hallazgo de la curva dosis-respuesta al agonista beta, isoproterenol, no se vióalterada por la presencia del prazosín, apoya la hipótesis de que el subtipo alfa1 de receptores adrenérgicos, media la respuesta salival simpática.In the present report, the identification of the subtype alpha-adrenoceptor which mediates the secretory responses in the rat's submaxilary gland, was estudied. For this purpose, the secretory responses to the sympathetic neurotransmitter, noradrenaline, were determined in the presence of different doses of selective alfa1 adrenergic antagonists (prazosin); in the presence of alfa2 selective adrenergic antagonists (yohimbine) and after administration of a non selective adrenergic antagonist (phentolamine). In both, normally innervated as well as in chronic sympathetically denervated glands, the parameters studied were the following: 1) shift of the dose-response curves; 2) DE20 ,ul and 3) pA2 determination. From the results obtained it is concluded that the alfa1 subtype of adrenoceptors mediates the sympathetic secretory responses in the submaxillary gland. This interpretation is further supported by the finding that the response to the beta agonist, isoproterenol, were unchaged after administration of different doses of prazosin.Facultad de Ciencias Veterinaria
The SMG of mice and rats contain a heterologous group of biologically active factors. Some are we... more The SMG of mice and rats contain a heterologous group of biologically active factors. Some are well known, can be obtained at high purity and are well-characterized. There is strong evidence for the presence of others although they have not been purified. Finally, some of them are questionable and/or have not yet been characterized. EPO would be one of the factors whose presence in the SMG is strongly suspected, although its biological activity has not been demonstrated yet. Its presence in the gland, therefore, is only supported by radioimmunoassay data and immunocytochemical methods. Immunoreactive EPO is undetectable in the mouse SMG until the 30th day of postnatal life, increasing thereafter at a uniform rate and reaching adult levels by 50-60 days of age. The parallelism between its concentration in extracts of the gland, the size and relative proportion of GCT cells, could be accepted as indirect evidence for its localization in these cells. The rise in iEPO concentration in SMGs after androgen treatment, its fall following orchiectomy, and its reduction after duct ligation in proportion to the degree of degranulation of GCT cells lend support to the above hypothesis. Salivary secretions induced by either NE or ISO contain high levels of iEPO. A significant depletion of gland content is also observed. These two sets of data indicate that SMG exocrine iEPO secretion occurs and that this secretion is mediated by adrenergic receptors. The question whether the SMG also functions as an endocrine organ in relation to EPO can not be answered at present.
The alpha adrenoceptor that mediates the secretory responses to norepinephrine in submaxillary gl... more The alpha adrenoceptor that mediates the secretory responses to norepinephrine in submaxillary glands was characterized. All three alpha antagonists employed produced in innervated glands parallel displacements of the dose-response curves to norepinephrine, prazosin being 30 and 100 times more potent than phentolamine and yohimbine, respectively. Chronic sympathetic denervation produced supersensitivity to norepinephrine. Under these conditions prazosin also was more potent than yohimbine but the shifts of the dose-response curves to norepinephrine were nonparallel. Potentiation of norepinephrine by cocaine did not modify the effects of prazosin in innervated glands. The nonparallel displacements observed in denervated glands were related to the development of postjunctional supersensitivity of the beta adrenoceptor-mediated responses because after administration of propranolol the displacements produced by prazosin were parallel. Responses to methoxamine were not potentiated by denervation and were competitively antagonized by prazosin in both innervated and denervated glands. Specific [3H]clonidine binding to membranes of submaxillary glands showed at least two independent sites with a KD1 of 0.37 nM and a KD2 of 65 nM. The number of sites of each component was doubled after chronic sympathetic denervation. Binding of [3H]prazosin (KD, 0.43 nM; maximum binding sites, 78.5 fmol/mg of protein) was not affected by denervation. The present findings show that sialagogue responses to sympathomimetic agents are mediated by alpha-1 adrenoceptor activation in both innervated and denervated submaxillary glands. Chronic sympathetic denervation does not produce postjunctional supersensitivity of the alpha-1-mediated responses and the supersensitivity of the beta-mediated responses interferes with determinations of dose-response curves to the sympathetic neurotransmitter.
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright
La obturacion de los conductos radiculares consiste en el relleno permanente del “espacio endodon... more La obturacion de los conductos radiculares consiste en el relleno permanente del “espacio endodontico” y el reemplazo del contenido normalo patologico del conducto por materiales que deben estar bien compactados y adaptados a las paredes del mismo. Al ser imposible la desinfeccion total de los conductos radiculares, es evidente la necesidad de utilizar un sellador endodontico con accion bactericida, o al menos bacteriostatica, que pueda actuar contra las bacterias que persisten luego de la preparacion quirurgica del conducto radicular. El objetivo de este estudio fue evaluar in vitro el poder antiseptico del cemento de Grossman, un material de obturacion muy utilizado en endodoncia, en combinacion con 2 proporciones de yodoformo, sobre bacterias comunmente encontradas en infecciones de origen endodontico. Resultados: el yodoformo puro no evidencio capacidad antiseptica sobre ninguna de las cepas estudiadas. Sin embargo, al asociarse con CG incremento su efecto inhibitorio sobre Stre...
El presente trabajo aporta evidencia de la presencia de receptores de cannabinoides en la glandul... more El presente trabajo aporta evidencia de la presencia de receptores de cannabinoides en la glandula submaxilar de la rata, cuya expresion secircunscribe a componentes acinares y ductales. A su vez, los resultados expuestos confirman la participacion de los receptores de cannabinoides en el control de la secrecion salival, y por ende aportan una explicacion empirica a la hiposialia observada luego del consumo de marihuana (AU) The present study provides evidence for the presence of cannabinoid receptors in rat submandibular gland, whose expression is restricted to acinar and ductal components. In turn, the presented results confirm the involvement of cannabinoid receptors in the control of salivary secretion, and thus provide an empirical explanation to hyposialia observed after marijuana consumption. (AU)
anandamide (6 ! 10-5 M) on salivary secretion. Lipopolysaccharide (5 mg/kg/3 h) injected intraper... more anandamide (6 ! 10-5 M) on salivary secretion. Lipopolysaccharide (5 mg/kg/3 h) injected intraperitoneally and ethanol (3 g/kg/1 h) injected intragastrically inhibited the salivary secretion induced by the sialogogue metacholine; this inhibitory effect was blocked by CB1 and/or CB2 receptor antagonists. Similar to the hypothalamus, these effects seem to be mediated by increased anandamide. In summary, similar mechanisms mediate the inhibitory actions of endocannabinoids and cannabinoids in both hypothalamus and submandibular gland during drug consumption and inflammation.
The aims of the present study were, first, to identify signs of alveolar bone damage in early sta... more The aims of the present study were, first, to identify signs of alveolar bone damage in early stages of experimental periodontitis (EP) and, second, to assess its possible prevention by treatment with cannabinoid receptor 2 agonist HU 308. Experimental periodontitis was induced by injections of lipopolysaccharide (LPS) (1mg/ml) in gums surrounding maxillary and mandibular first molar, 3 days per week, and untreated controls were kept for comparison. Then, a 3-week study was conducted including eighteen new rats (six rats per group): 1) controls; 2) experimental periodontitis rats; and 3) experimental periodontitis rats treated daily with HU 308 (500 ng/ml). After euthanasia, alveolar bone loss was assessed by morphometric and histomorphometric techniques, and the content of prostaglandin E 2 (PGE 2) in gingival tissue was evaluated by radioimmunoassay. The first signs of alveolar bone loss were apparent at 3 weeks of experimental periodontitis (ρ<0.05) in the mandibular first molar, but there was no detectable change at 1 week, leading us to establish 3 weeks as an early stage of experimental periodontitis. Rats subjected to 3-week experimental periodontitis showed less interradicular bone volume, less whole bone perimeter and fewer bone formation areas, and higher periodontal space height, bone resorption areas, number of osteoclasts and gingival content of prostaglandin E 2 than controls, while HU 308 prevented, at least partially, the deleterious effects (ρ<0.001). We can conclude that a 3-week term of lipopolysaccharide-induced periodontitis in rats provides a valid model of the early stage of the disease, as emerging damage is observed in bone tissue. Furthermore, harmful effects at 3 weeks could be prevented by local stimulation of cannabinoid receptor 2, before greater damage is produced.
Objective: Mild and chronic energy restriction results in growth retardation with puberal delay, ... more Objective: Mild and chronic energy restriction results in growth retardation with puberal delay, a nutritional disease known as nutritional dwarfing (ND). The aim of the present study was to assess the profile of hypothalamic luteinizing hormone-releasing hormone (LHRH) release, at baseline and under glutamate stimulation, in ND rats to elucidate gonadotrophic dysfunction. Reproductive ability during refeeding was also studied. Material and methods: At weaning, 60 male rats were assigned to two groups of 30 animals each: a control and an experimental group. Control rats were fed ad libitum with a balanced rodent diet. The experimental group received 80% of the diet consumed by the control group for 4 weeks. After 4 weeks of food restriction, the ND group was fed freely for 8 weeks. Ten rats from each group were sacrificed every 4 weeks for assays. Results: At week 4, body weight and length were significantly diminished in the experimental group vs. the control group (po0.001). No changes were observed in LHRH baseline release, pulse frequency or amplitude in the experimental group compared with the control group at any time. However, under glutamate stimulation, LHRH release was significantly higher in ND rats than in control rats at week 4 (po0.05). Refeeding the ND group allowed the rats to reach overall growth and reproductive ability. Conclusions: The results of the present study suggest that the response to the facilitatory effect of glutamate on LHRH release in post-restricted ND rats is probably related to a lesser central nervous system maturation in relation to their chronological age. The adequate somatic growth and normal reproductive ability attained with refeeding suggest the reversibility of the two energetically costly processes compromised by global, mild and chronic food restriction.
The effects of sub-chronic cadmium (Cd) administration on the structure and subsequent secretory ... more The effects of sub-chronic cadmium (Cd) administration on the structure and subsequent secretory responses of the submaxillary and parotid glands to sialagogues were investigated. Female Wistar rats were injected subcutaneously with cadmium chloride (3.0 mg/kg body weight), 4 times a week for 2, 3 or 4 weeks. Functional and histopathological studies were done 3 days after the last injection, Dose-response curves for norepinephrine and methacholine were obtained. After 2 weeks of Cd administration significant changes in the secretory response to these sialogogues were observed. The dose-response curves after pretreatment with Cd for 3 weeks were also shifted to the right, but the response showed recovery when compared with that of 2-week treated animals. Parotid amylase concentration was also diminished by Cd. Treated rats had reduced acinar diameters, and an increase in acinar cell nuclei per field in both the submaxillary and parotid glands. Thus sub-chronic administration of ionized Cd produces morphological and functional changes in rat salivary glands. Moreover, the extent of tubular and acinar damage matches the degree of gland dysfunction as judged by the diminution of secretory responses to sialagogues
Background: Transient receptor potential vanilloid type-1 (TRPV1) is expressed in oral tissues ce... more Background: Transient receptor potential vanilloid type-1 (TRPV1) is expressed in oral tissues cells and its activity can be regulated by inflammation products and anandamide. The aim of the present study was to evaluate the effects of blocking TRPV1 or specific cannabinoid receptors 1 (CB1r) and 2 (CB2r) on periodontal status of rats subjected to experimental periodontitis (EP). Methods: Male rats were distributed in groups 1) control, 2) lipopolysaccharide induced EP (LPS) and 3) LPS plus capsazepine (Capz, TRPV1 antagonist) application (LPS+Capz). EP was induced by injections of LPS (1 mg/ml) around first molars and treatment was performed with Capz (2 ug/ml) applied locally during six weeks. Additional experiment was performed by applying CB1r and CB2r antagonists (AM251 and AM630) to rats with EP. Results: Capz prevented alveolar bone loss (ABL) on the external crests and in the interradicular bone of the first molars (Periodontal space height: LPS, 270.7±33.5µm versus LPS+Capz, 216.4±19.9µm; ρ<0.01). Inflammatory mediators, like tumor necrosis factor alpha (TNFα) and prostaglandin E 2 (PGE 2), increased by LPS-induced EP, were diminished in gingival tissue of rats treated with Capz. In contrast, application of AM251 and AM630 exacerbated ABL and gingival inflammatory mediators, increased by LPS, altering also biomechanical properties. Conclusions: TRPV1 blockade attenuates periodontal impairment in EP rats, since it reduces local inflammation, unlike CB1r and CB2r blockade. This work lays the foundations for developing This article is protected by copyright. All rights reserved. therapeutics in humans based on the pharmacological manipulation of these receptors to treat periodontal disease.
regulation of submandibular gland secretion in the rat Endothelins participate in the central and... more regulation of submandibular gland secretion in the rat Endothelins participate in the central and peripheral You might find this additional info useful... 40 articles, 10 of which can be accessed free at:This article cites
The aims of the present study were, first, to identify signs of alveolar bone damage in early sta... more The aims of the present study were, first, to identify signs of alveolar bone damage in early stages of experimental periodontitis (EP) and, second, to assess its possible prevention by treatment with cannabinoid receptor 2 agonist HU 308. Experimental periodontitis was induced by injections of lipopolysaccharide (LPS) (1mg/ml) in gums surrounding maxillary and mandibular first molar, 3 days per week, and untreated controls were kept for comparison. Then, a 3-week study was conducted including eighteen new rats (six rats per group): 1) controls; 2) experimental periodontitis rats; and 3) experimental periodontitis rats treated daily with HU 308 (500 ng/ml). After euthanasia, alveolar bone loss was assessed by morphometric and histomorphometric techniques, and the content of prostaglandin E2 (PGE2) in gingival tissue was evaluated by radioimmunoassay. The first signs of alveolar bone loss were apparent at 3 weeks of experimental periodontitis (ρ<0.05) in the mandibular first molar...
American Journal of Physiology-Endocrinology and Metabolism, 2001
Inducible (calcium-independent) nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are imp... more Inducible (calcium-independent) nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are important in the regulation of the function of different organs during infection. A single dose of lipopolysaccharide (LPS; 5 mg/kg ip) within 6 h increased NOS activity (20%) and prostaglandin E (PGE) content (100%) in submandibular glands (SMG) and blocked stimulated salivary secretion in adult male rats. The administration of an iNOS synthesis inhibitor, aminoguanidine (AG), with LPS decreased NOS activity and PGE content. Furthermore, the administration of meloxicam (MLX), an inhibitor of COX-2, blocked the increase in PGE and the production of NO. The incubation of slices of SMG in the presence of 3-morpholinosydnonimine, a donor of NO, increased the release of PGE highly significantly. The incubation of SMG in the presence of a PGE1 analog (alprostadil) increased the production of NO. These results indicate that LPS activates NOS, leading to NO release, which activates COX, generating...
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, Mar 10, 2018
Saliva is very important to oral health, and a salivary deficit has been shown to bring serious p... more Saliva is very important to oral health, and a salivary deficit has been shown to bring serious problems to oral health. There is scant information about the mechanisms through which salivary glands participate in post-tooth extraction socket healing. Therefore, the aim of the present study was to investigate the effect of submandibulectomy (SMx), consisting of the ablation of submandibular and sublingual glands (SMG and SLG, respectively), on PGE signaling and other bone regulatory molecules, such as OPG and RANKL, involved in tooth extraction socket healing. Male Wistar rats, 70 g body weight, were assigned to an experimental (subjected to SMx) or a control group (sham operated). One week later, the animals in both groups underwent bilateral extraction of the first mandibular molars. The effect of SMx on different stages of socket healing after tooth extraction (7, 14, and 30 days) was studied by evaluating some parameters of inflammation, including PGE and its receptors, and of b...
It is known that marijuana use decreases saliva secretion. Therefore, we hypothesized that cannab... more It is known that marijuana use decreases saliva secretion. Therefore, we hypothesized that cannabinoid receptors (CBs) are located in salivary glands to mediate that effect. In these experiments, we used the submandibular gland (SMG) of male rats, which is one of the major salivary glands. Mammalian tissues contain at least two types of CBs, CB1 and CB2, mainly located in the nervous system and peripheral tissues, respectively. Both receptors are coupled to Gi protein and respond by inhibiting the activity of adenylyl cyclase. We demonstrated that both CB1 and CB2 are present in the SMG, each showing specific localizations. The best-known endocannabinoid is anandamide (AEA), which binds with high affinity to CB1 and CB2. We showed that AEA markedly reduced forskolin-induced increase of cAMP content in vitro. This effect was blocked by AM251 and AM630 (CB1 and CB2 antagonists, respectively), indicating that both receptors are implicated in SMG physiology. In addition, we showed that ...
It is known that immune challenge inhibits reproductive function and that endocannabinoids (eCB) ... more It is known that immune challenge inhibits reproductive function and that endocannabinoids (eCB) modulate sexual hormones. However, no studies have been performed to assess whether the endocannabinoid system mediates the inhibition of hormones that control reproduction due to immune system activation during systemic infections. For that reason, we evaluated the participation of the hypothalamic cannabinoid receptor CB1 on hypothalamic-pituitary-gonadal (HPG) axis activity in rats submitted to immune challenge. Male adult rats were treated via intracerebroventricular (i.c.v.) administration with a CB1 antagonist/inverse agonist, (AM251, 500 ng/5 ul), followed by an intraperitoneal (i.p.) injection of lipopolysaccharide (LPS, 5 mg/kg) 15 min later. Plasmatic, hypothalamic and adenohypophyseal pro-inflammatory cytokines, hormones and neuropeptides were assessed 90 or 180 min post-LPS. Plasma concentration of TNFα and adenohypophyseal mRNA expression of Tnfα and Il1β increased 90 and 18...
Se identificó el subtipo alfa1 adrenoceptores como mediador de la respuesta secretoria en la glán... more Se identificó el subtipo alfa1 adrenoceptores como mediador de la respuesta secretoria en la glándula submaxilar de la rata, basándose en el empleo de diferentes dosis de antagonistas adrenérgicos selectivos alfa1 (prazosín), alfa2 (yohimbina) y no selectivo (fenatolamina) ante la acción del neurotransmisor, la noradrenalina. Los parámetros determinados tanto en glándulas normales como crónicamente desnervadas fueron: a) desplazamientos de las curvas dosis-respuesta; b) dosis efectiva 20 microlitros (DE20 ,ul) y c) determinación del pA2. El hallazgo de la curva dosis-respuesta al agonista beta, isoproterenol, no se vióalterada por la presencia del prazosín, apoya la hipótesis de que el subtipo alfa1 de receptores adrenérgicos, media la respuesta salival simpática.In the present report, the identification of the subtype alpha-adrenoceptor which mediates the secretory responses in the rat's submaxilary gland, was estudied. For this purpose, the secretory responses to the sympathetic neurotransmitter, noradrenaline, were determined in the presence of different doses of selective alfa1 adrenergic antagonists (prazosin); in the presence of alfa2 selective adrenergic antagonists (yohimbine) and after administration of a non selective adrenergic antagonist (phentolamine). In both, normally innervated as well as in chronic sympathetically denervated glands, the parameters studied were the following: 1) shift of the dose-response curves; 2) DE20 ,ul and 3) pA2 determination. From the results obtained it is concluded that the alfa1 subtype of adrenoceptors mediates the sympathetic secretory responses in the submaxillary gland. This interpretation is further supported by the finding that the response to the beta agonist, isoproterenol, were unchaged after administration of different doses of prazosin.Facultad de Ciencias Veterinaria
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