American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1982
Physiological changes accompanying a period of voluntary hypophagia in male Sprague-Dawley rats a... more Physiological changes accompanying a period of voluntary hypophagia in male Sprague-Dawley rats after insulin-induced hyperphagia and body weight gain were investigated. Postinsulin hypophagia was manifested as a reduction in meal duration diurnally and nocturnally (Geary et al., Behav. Neural Biol. 31: 435-442, 1981). Gastrointestinal transit of 14C-labeled nutrients was unchanged in hypophagic rats, suggesting a postabsorptive mechanism controlled the hypophagia. Basal blood glucose and plasma nonesterified fatty acids, 3-hydroxybutyrate, glycerol, and some amino acids were elevated during hypophagia, while liver glycogen content was reduced. Hypophagic rats' arteriovenous blood glucose differences and glucose oxidation rates, however, were not different from controls. After nutrient repletion blood glucose and plasma glycerol remained elevated in hypophagic rats in comparison to controls, while differences in other plasma metabolites were reduced. Liver glycogen accumulated f...
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1982
The effects of feeding on liver glycogen content and blood glucose in the hepatic and hepatic por... more The effects of feeding on liver glycogen content and blood glucose in the hepatic and hepatic portal veins were investigated in rats. Liver glycogen content decreased about 25% during meals both in rats refed after 12 h food deprivation (23 +/- 1 to 17 +/- 1 mg glycogen/g liver) and in ad libitum-fed rats taking fully spontaneous meals (44 +/- 2 to 32 +/- 2 mg/g). Liver glycogen began to increase within 30 min after meals in ad libitum-fed rats. Hepatic vein blood glucose levels at meal onset (118 +/- 4 mg/dl in the food-deprived rats, 127 +/- 4 in ad libitum-fed rats) and at meal end (155 +/- 3 and 166 +/- 5 mg/dl, respectively) were similar in the two groups. Portal vein blood glucose increased during meals in the previously food-deprived rats (83 +/- 4 to 116 +/- 6 mg/dl) but not in the ad libitum-fed rats (127 +/- 5 to 132 +/- 3 mg/dl). Mechanisms that may elicit prandial glycogenolysis and the possible role of this effect in the production of meal ending satiety are discussed.
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1981
The suppression of food intake elicited in rats by injection of pancreatic glucagon and the accom... more The suppression of food intake elicited in rats by injection of pancreatic glucagon and the accompanying changes in energy metabolite flux were investigated. Glucagon injections, 120-360 micrograms ip, were made as rats began the first meal of the dark phase after food deprivation during the light phase. Glucagon-injected rats terminated their meals sooner and ate smaller meals than vehicle-injected rats. For metabolic assays, rats were identically treated and killed just at meal onset or 15 min later. Portal vein blood glucose increased similarly in all rats allowed to feed, whereas plasma nonesterified fatty acid and D-(-)-3-hydroxybutyrate levels decreased during feeding. In contrast, hepatic vein and aorta blood glucose levels increased more after glucagon than after vehicle injections. Liver glycogen content decreased after glucagon injections. The highest glucagon dose only had slight lipolytic and ketogenic effects. It was concluded the glycogenolytic and hyperglycemic action...
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1998
Abdominal vagal and splanchnic afferents play an important role in the control of food intake in ... more Abdominal vagal and splanchnic afferents play an important role in the control of food intake in that they transmit various satiety signals to the central nervous system. Inasmuch as previous studies have shown that the anorectic effect of intraperitoneally injected amylin was not abolished by subdiaphragmatic vagotomy, the aim of the present study was to elucidate the role of splanchnic afferents in mediating amylin’s anorectic effect after intraperitoneal injection. Rats were pretreated intraperitoneally with the neurotoxin capsaicin, which destroys primary sensory (vagal and splanchnic) afferents. Sham-treated rats served as control. Capsaicin-pretreatment had no influence on the anorectic effects of amylin (5 μg/kg) and the related peptide, calcitonin gene-related peptide (CGRP; 5 μg/kg), in 24-h food-deprived rats. Abolition of cholecystokinin’s (3 μg/kg) anorectic effect agrees with previous studies and confirmed the effectiveness of the capsaicin pretreatment. In conclusion, ...
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1999
In former work, intraperitoneal injection of 2-mercaptoacetate (MA), an inhibitor of fatty acid o... more In former work, intraperitoneal injection of 2-mercaptoacetate (MA), an inhibitor of fatty acid oxidation, increased food intake in rats, which was attenuated by hepatic branch vagotomy, and intraportal injection of MA increased the discharge rate in hepatic vagal afferents. In the present study, we investigated, whether intraperitoneal injection or intraportal infusion of MA affects the hepatic membrane potential in rats in vivo. The liver cell membrane potential was measured in anesthetized Sprague-Dawley rats with the microelectrode technique. Intraperitoneal injection of MA at a dose of 800 μmol/kg body wt significantly decreased the hepatocyte membrane potential by 3.8 mV, whereas at a dose of 400 μmol/kg, the depolarization (1.5 mV) of the membrane was not significant. In another strain of Sprague-Dawley rats, however, MA (400 μmol/kg) produced a significant depolarization of the hepatocyte membrane 50 min (2.6 mV) and 2 h (2.9 mV) after intraperitoneal injection. Intraportal ...
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2001
We investigated the role of histamine H1 receptors in mediating the anorectic effect of intraperi... more We investigated the role of histamine H1 receptors in mediating the anorectic effect of intraperitoneally injected amylin (5 and 20 μg/kg), the amylin agonist salmon calcitonin (sCT; 10 μg/kg), leptin (1.3 mg/kg), and cholecystokinin (CCK; 20 μg/kg). The experiments were performed with mice lacking functional H1 receptors (H1Rko) and wild-type (WT) controls. The mice were also injected with the H3 antagonist thioperamide (20 mg/kg), which reduces feeding by enhancing the release of endogenous histamine through presynaptic H3 receptors. The feeding-suppressive effect of thioperamide was abolished in H1Rko mice. The anorectic effects of amylin and sCT were significantly reduced in 12-h food-deprived H1Rko mice compared with WT mice [1-h food intake: WT-NaCl 0.51 ± 0.05 g vs. WT-amylin (5 μg/kg) 0.30 ± 0.06 g ( P < 0.01); H1Rko-NaCl 0.45 ± 0.05 g vs. H1Rko-amylin 0.40 ± 0.04 g; WT-NaCl 0.40 ± 0.09 g vs. WT-sCT (10 μg/kg) 0.14 ± 0.10 g ( P < 0.05); H1Rko-NaCl 0.44 ± 0.08 g vs. H1R...
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2001
The anorectic effect of the pancreatic peptide amylin has been established in numerous studies. H... more The anorectic effect of the pancreatic peptide amylin has been established in numerous studies. Here, we investigated the influence of a pretreatment with dopamine (DA) D1- and D2-receptor antagonists on the anorectic effect of intraperitoneally injected amylin in rats fed a medium-fat (18% fat) diet. In 24-h food-deprived rats, pretreatment with the DA D2-receptor antagonist raclopride [100 μg/kg (0.2 μmol/kg) ip] significantly attenuated amylin's (5 μg/kg ip) anorectic effect, whereas raclopride alone had no effect on food intake [i.e., food intakes 1 h after injection were ( n = 12): NaCl/NaCl 7.3 ± 0.5 g; NaCl/amylin 3.9 ± 0.6; raclopride/NaCl 7.7 ± 0.7; raclopride/amylin 5.6 ± 0.7]. Pretreatment with another DA D2 receptor antagonist, sulpiride [50 mg/kg (154 μmol/kg) ip], similarly reduced amylin's satiety effect, whereas pretreatment with the DA D1-receptor antagonist SCH-23390 [10 μg/kg (0.03 μmol/kg) ip] did not influence amylin's effect. SCH-23390, however, com...
decreases meal size in rats. PHYSIOL BEHAV 58(6) 1197-1202, 1995.-Adult male rats were intraperit... more decreases meal size in rats. PHYSIOL BEHAV 58(6) 1197-1202, 1995.-Adult male rats were intraperitoneally (IP) injected with 1.0 pg/kg amylin at the beginning of the dark phase in 24 h food deprived or undeprived rats, and a computerized system measured feeding behavior. In food deprived rats, amylin reduced the size of the first postdeprivation meal without affecting intrameal feeding rate or the size or timing of subsequent meals. The same pattern was observed in undeprived rats, but amylin also increased the latency to the first postinjection meal. In a conditioned taste aversion test, IP amylin (1/xg/kg) injection just prior to rats' first access to a saccharine-flavored version of their maintenance diet, failed to affect their subsequent selection of that diet relative to the maintenance diet 2 d later. Finally, 2-min meal-contingent hepatic portal infusions of amylin (1-3.2 /zg/rat) during nocturnal spontaneous meals in undisturbed, ad lib fi~d rats reduced the meal size and meal duration, and increased the postprandial satiety ratio. Again, feeding rate and the size and duration of subsequent meals were not affected. These results suggest that amylin inhibits feeding by facilitating meal-ending satiety processes. Amylin Food intake Meal patterns Spontaneous feeding Rat Conditioned taste aversion Postprandial satiety
In monogastric species, a considerable portion of amino acid nitrogen is absorbed across the brus... more In monogastric species, a considerable portion of amino acid nitrogen is absorbed across the brush-border membrane of the small intestine as small peptides (e.g., tripeptides and dipeptides). In ruminants, however, this process is less clear. Therefore, we investigated the uptake of radioactively labeled glycylsarcosine as a model dipeptide across the intestinal brush-border membrane using brush-border membrane vesicles prepared from the bovine small intestine. Uphill transport of glycylsarcosine was energized by a transmembrane H+ gradient and was further stimulated by an electrical potential difference across the membrane. Transport mediated by a carrier contributes to total glycylsarcosine transport across the brush-border membrane. Comparison of the apparent kinetic constants between brush-border membranes prepared from the proximal jejunum or ileum revealed similar half-saturating substrate concentrations (1.28 and 0.93 mmol/L for proximal jejunum and ileum, respectively), but maximal transport rates appeared to be somewhat higher in the proximal small intestine (2.15 and 1.20 nmol/mg of protein per 3 s for proximal jejunum and ileum, respectively). Uptake of glycylsarcosine was strongly inhibited by other dipeptides, but the amino acids glycine and sarcosine did not affect transport. Inhibition of glycylsarcosine uptake by cephalexin indicated an affinity of the carrier for cephalosporin antibiotics. Transport of intact dipeptides across the brush-border membrane of the small intestine might be of physiological importance in ruminants because the microbial and dietary proteins resistant to rumen degradation are digested and absorbed in the small intestine.
Pflügers Archiv - European Journal of Physiology, 1981
The kinetics of [3H]hypoxanthine entry into lamb mid-jejunum were measured using 2-rain mucosal e... more The kinetics of [3H]hypoxanthine entry into lamb mid-jejunum were measured using 2-rain mucosal exposures. Mucosal hypoxanthine uptake occurred by a Na +-and energy-dependent saturable mechanism indicating that a carrier-mediated active transport process is involved. Inhibitory measurements indicate that hypoxanthine, adenosine, uracil and thymine compete for a common entry mechanism. Adenine, uric acid, allantoine and thymidine produced no significant inhibition of hypoxanthine entry. In additional experiments hypoxanthine was transported against a high concentration gradient from the mucosal to the serosal side of everted sacs of mid-jejunum. Therefore hypoxanthine appears to be absorbed by active transport from the lamb jejunum.
OBJECTIVE: Neurons in the area postremaanucleus of the solitary tract (APaNTS) region mediate amy... more OBJECTIVE: Neurons in the area postremaanucleus of the solitary tract (APaNTS) region mediate amylin's anorectic effect elicited by a single intraperitoneal (i.p.) injection of a low dose (5 mgakg). Here, we tested if a sustained elevation in amylin levels which was achieved by chronic amylin infusion reduces food intake by acting in the APaNTS region or, possibly, at other brain sites. Further, we tested the role of the APaNTS region in mediating the anorectic effects of high doses of amylin and its receptor agonist salmon calcitonin (sCT) after an acute single injection. DESIGN: Amylin (2 mgakgah) was chronically infused i.p. by osmotic minipumps in APaNTS-lesioned (AP-X) or sham-lesioned (SHAM) rats. For the acute experiments, amylin or sCT was injected i.p. at doses of 0.5 (only sCT), 5 or 50 mgakg. Food intake was measured by a computerized system. Body weight was assessed by manually weighing the rats. RESULTS: Amylin signi®cantly reduced cumulative food intake for about 7 days in SHAM but not in AP-X rats. Amylin's effect in SHAM rats was mainly due to a reduction of the size of nocturnal meals (eg average meal size during the ®rst four dark phases; SHAM, NaCl 4.1 AE 0.6 vs amylin 2.6 AE 0.4 g; n 6, P`0.05; AP-X, 2.6 AE 0.3 vs 3.7 AE 0.3) while light phase food intake was unaffected. Body weight gain over the whole 14 day infusion period was reduced by amylin in SHAM (NaCl 61 AE 6 vs amylin 46 AE 4 g; P`0.05) but not in AP-X rats (54 AE 4 vs 62 AE 4). After single injection, the anorectic effect of high doses of amylin and sCT (50 mgakg) was attenuated, but not abolished, in AP-X rats. CONCLUSION: We conclude that, under our experimental conditions, neurons in the APaNTS region are necessary for chronically elevated peripheral amylin to reduce food intake in rats. High doses of amylin, however, may be able to overrun these receptors and reduce feeding by acting at other brain sites.
Tricarballylic acid is a non-metabolizable rumen bacterial fermentation product of the naturally ... more Tricarballylic acid is a non-metabolizable rumen bacterial fermentation product of the naturally occurring tricarboxylic acid trans-aconitic acid. The aim of the present study was to investigate intestinal absorption of tricarballylate using brush-border membrane vesicles (BBMVs) isolated from the proximal jejunum of steers by a Ca2+ precipitation method with subsequent differential centrifugation. Transport of tricarballylate was investigated indirectly (influence of tricarballylate on the uptake of 14C-labelled citrate) as well as directly (uptake of 3H-labelled tricarballylate). Citrate as well as tricarballylate uptake (at a concentration of 0.05 mmol l-1) was strongly stimulated by an inwardly directed initial Na+ gradient. Furthermore, transport of both tricarboxylates under Na+ gradient conditions was clearly enhanced by lowering the extravesicular pH from 7.8 to 5.6. The imposition of an inwardly directed H+ gradient (pH(out)/pH(in) = 5.6/7.8) further enhanced the intravesicular accumulation of citrate as well as of tricarballylate compared with pH(out)/pH(in) = 5.6/5.6. Unequivocal evidence for a common transport site for tricarballylate and citrate was obtained from &#39;cis-inhibition&#39; and &#39;trans-stimulation&#39; of Na(+)-dependent citrate uptake by tricarballylate. In further experiments the influence of different substances on the uptake of 3H-labelled tricarballylate was evaluated. Unlabelled tricarballylate, citrate, succinate as well as trans- and cis-aconitate significantly inhibited the accumulation of 3H-labelled tricarballylate by BBMVs. Tricarballylate uptake as a function of the tricarballylate concentration revealed a Na(+)-dependent saturable component (apparent kinetic parameters: maximal transport capacity (Vmax) = 119 pmol (mg protein)-1 (3s)-1; affinity constant (Km) = 0.097 mmol l-1) and a Na(+)-independent diffusional component (diffusion constant: 169 nl (mg protein)-1 (3s)-1). It is concluded that tricarballylate and citrate are transported across the intestinal brush-border membrane by a common, Na(+)-dependent transport mechanism. The stimulatory influence of a low extravesicular pH most probably indicates that the protonated forms of tricarboxylates are better transported than the trivalent species.
Changes in food intake, body weight, and meal patterns brought about by repeated injections of in... more Changes in food intake, body weight, and meal patterns brought about by repeated injections of insulin were investigated. Male Sprague-Dawley albino rats were subcutaneously injected with slow-acting insulin twice daily for 3 days, 4 IU/injection on Day 1 and 6 IU/injection thereafter. Food intake and body weight were increased by the injections. Hyperphagia was most marked during the bright phase of the lighting cycle. Meal frequency increased during both lighting phases and nocturnal meal duration decreased, resulting in disappearance of the normal circadian rhythmicity of feeding. Postinsulin, food intake and body weight decreased. Body weight returned to control levels within 48 hr after insulin treatment, although the net hypophagia during this time failed to match the degree of the preceding hyperphagia. Postinsulin hypophagia, manifested primarily as a reduction in meal duration, was evident in both lighting phases. The data suggest that both behavioral and metabolic adaptations contribute to the renormalization of body weight following insulin treatments and that different controls of food intake operate during insulin hyperphagia and postinsulin hypophagia.
Mucosal uptake of succinate across the luminal epithelial border in various segments of the large... more Mucosal uptake of succinate across the luminal epithelial border in various segments of the large intestine of the rat (proximal and distal colon, caecum) was investigated using an in vitro mucosal uptake technique. For comparison, some experiments with jejunal preparations were also performed. Additionally, disappearance of succinate from the lumen of ligated loops of the proximal and distal colon was measured in vivo. In the ligated loop experiments, the succinate concentration of the instilled solution significantly decreased during a period of 30 min in both colonic segments, indicating absorption of succinate. The in vitro experiments revealed a distinct Na+ dependence of mucosal succinate uptake in all intestinal segments investigated. Because succinate uptake by the colonic mucosa of germ‐free rats was similarly enhanced in the presence of Na+ compared with Na(+)‐free conditions, measured uptake appears to be due to mucosal uptake rather than to Na(+)‐dependent uptake of succ...
data from our laboratory indicate that deeper, more mesial discharges may also be recorded neurom... more data from our laboratory indicate that deeper, more mesial discharges may also be recorded neuromagnetically. These results demonstrate that by neuromagnetic mapping of interictal spikes in the human brain it is possible to identify with precision the three-dimensional location of intracortical sources producing epileptiform discharges. Further analyses of the orientation, polarity, and timing of these fields, coupled with detailed postsurgical histological data, may provide insight about rapidly occurring cellular events underlying interictal spiking.
We tested whether pancreatic glucagon&#39;s effects on satiety and hepatic glycogenolysis dep... more We tested whether pancreatic glucagon&#39;s effects on satiety and hepatic glycogenolysis depend on variations in the macronutrient composition of the diet. Rats were kept on high carbohydrate, high fat, or high protein diets (HC-, HF- or HP-rats, respectively) and adapted to a 5 hour feeding (11:00-16:00)-19 hour deprivation (16:00-11:00) schedule. Glucagon (540 mcg/kg body weight) was intraperitoneally injected at 14:00. Glucagon stimulated similar amounts of hepatic glycogenolysis in HC- and in HF-rats and less glycogenolysis in HP-rats, but glucagon decreased food intake only in HC-rats. When HF- or HP-rats were prefed the HC-diet once for 1 hour (11:00-12:00) prior to injection, glucagon stimulated hepatic glycogenolysis similarly in both groups but decreased food intake only in HF-rats. Therefore, stimulation of hepatic glycogenolysis by glucagon is not sufficient to elicit satiety under all feeding conditions. The results also suggest that glucagon-induced satiety is not limited to carbohydrate intake.
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1982
Physiological changes accompanying a period of voluntary hypophagia in male Sprague-Dawley rats a... more Physiological changes accompanying a period of voluntary hypophagia in male Sprague-Dawley rats after insulin-induced hyperphagia and body weight gain were investigated. Postinsulin hypophagia was manifested as a reduction in meal duration diurnally and nocturnally (Geary et al., Behav. Neural Biol. 31: 435-442, 1981). Gastrointestinal transit of 14C-labeled nutrients was unchanged in hypophagic rats, suggesting a postabsorptive mechanism controlled the hypophagia. Basal blood glucose and plasma nonesterified fatty acids, 3-hydroxybutyrate, glycerol, and some amino acids were elevated during hypophagia, while liver glycogen content was reduced. Hypophagic rats' arteriovenous blood glucose differences and glucose oxidation rates, however, were not different from controls. After nutrient repletion blood glucose and plasma glycerol remained elevated in hypophagic rats in comparison to controls, while differences in other plasma metabolites were reduced. Liver glycogen accumulated f...
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1982
The effects of feeding on liver glycogen content and blood glucose in the hepatic and hepatic por... more The effects of feeding on liver glycogen content and blood glucose in the hepatic and hepatic portal veins were investigated in rats. Liver glycogen content decreased about 25% during meals both in rats refed after 12 h food deprivation (23 +/- 1 to 17 +/- 1 mg glycogen/g liver) and in ad libitum-fed rats taking fully spontaneous meals (44 +/- 2 to 32 +/- 2 mg/g). Liver glycogen began to increase within 30 min after meals in ad libitum-fed rats. Hepatic vein blood glucose levels at meal onset (118 +/- 4 mg/dl in the food-deprived rats, 127 +/- 4 in ad libitum-fed rats) and at meal end (155 +/- 3 and 166 +/- 5 mg/dl, respectively) were similar in the two groups. Portal vein blood glucose increased during meals in the previously food-deprived rats (83 +/- 4 to 116 +/- 6 mg/dl) but not in the ad libitum-fed rats (127 +/- 5 to 132 +/- 3 mg/dl). Mechanisms that may elicit prandial glycogenolysis and the possible role of this effect in the production of meal ending satiety are discussed.
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1981
The suppression of food intake elicited in rats by injection of pancreatic glucagon and the accom... more The suppression of food intake elicited in rats by injection of pancreatic glucagon and the accompanying changes in energy metabolite flux were investigated. Glucagon injections, 120-360 micrograms ip, were made as rats began the first meal of the dark phase after food deprivation during the light phase. Glucagon-injected rats terminated their meals sooner and ate smaller meals than vehicle-injected rats. For metabolic assays, rats were identically treated and killed just at meal onset or 15 min later. Portal vein blood glucose increased similarly in all rats allowed to feed, whereas plasma nonesterified fatty acid and D-(-)-3-hydroxybutyrate levels decreased during feeding. In contrast, hepatic vein and aorta blood glucose levels increased more after glucagon than after vehicle injections. Liver glycogen content decreased after glucagon injections. The highest glucagon dose only had slight lipolytic and ketogenic effects. It was concluded the glycogenolytic and hyperglycemic action...
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1998
Abdominal vagal and splanchnic afferents play an important role in the control of food intake in ... more Abdominal vagal and splanchnic afferents play an important role in the control of food intake in that they transmit various satiety signals to the central nervous system. Inasmuch as previous studies have shown that the anorectic effect of intraperitoneally injected amylin was not abolished by subdiaphragmatic vagotomy, the aim of the present study was to elucidate the role of splanchnic afferents in mediating amylin’s anorectic effect after intraperitoneal injection. Rats were pretreated intraperitoneally with the neurotoxin capsaicin, which destroys primary sensory (vagal and splanchnic) afferents. Sham-treated rats served as control. Capsaicin-pretreatment had no influence on the anorectic effects of amylin (5 μg/kg) and the related peptide, calcitonin gene-related peptide (CGRP; 5 μg/kg), in 24-h food-deprived rats. Abolition of cholecystokinin’s (3 μg/kg) anorectic effect agrees with previous studies and confirmed the effectiveness of the capsaicin pretreatment. In conclusion, ...
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1999
In former work, intraperitoneal injection of 2-mercaptoacetate (MA), an inhibitor of fatty acid o... more In former work, intraperitoneal injection of 2-mercaptoacetate (MA), an inhibitor of fatty acid oxidation, increased food intake in rats, which was attenuated by hepatic branch vagotomy, and intraportal injection of MA increased the discharge rate in hepatic vagal afferents. In the present study, we investigated, whether intraperitoneal injection or intraportal infusion of MA affects the hepatic membrane potential in rats in vivo. The liver cell membrane potential was measured in anesthetized Sprague-Dawley rats with the microelectrode technique. Intraperitoneal injection of MA at a dose of 800 μmol/kg body wt significantly decreased the hepatocyte membrane potential by 3.8 mV, whereas at a dose of 400 μmol/kg, the depolarization (1.5 mV) of the membrane was not significant. In another strain of Sprague-Dawley rats, however, MA (400 μmol/kg) produced a significant depolarization of the hepatocyte membrane 50 min (2.6 mV) and 2 h (2.9 mV) after intraperitoneal injection. Intraportal ...
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2001
We investigated the role of histamine H1 receptors in mediating the anorectic effect of intraperi... more We investigated the role of histamine H1 receptors in mediating the anorectic effect of intraperitoneally injected amylin (5 and 20 μg/kg), the amylin agonist salmon calcitonin (sCT; 10 μg/kg), leptin (1.3 mg/kg), and cholecystokinin (CCK; 20 μg/kg). The experiments were performed with mice lacking functional H1 receptors (H1Rko) and wild-type (WT) controls. The mice were also injected with the H3 antagonist thioperamide (20 mg/kg), which reduces feeding by enhancing the release of endogenous histamine through presynaptic H3 receptors. The feeding-suppressive effect of thioperamide was abolished in H1Rko mice. The anorectic effects of amylin and sCT were significantly reduced in 12-h food-deprived H1Rko mice compared with WT mice [1-h food intake: WT-NaCl 0.51 ± 0.05 g vs. WT-amylin (5 μg/kg) 0.30 ± 0.06 g ( P < 0.01); H1Rko-NaCl 0.45 ± 0.05 g vs. H1Rko-amylin 0.40 ± 0.04 g; WT-NaCl 0.40 ± 0.09 g vs. WT-sCT (10 μg/kg) 0.14 ± 0.10 g ( P < 0.05); H1Rko-NaCl 0.44 ± 0.08 g vs. H1R...
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2001
The anorectic effect of the pancreatic peptide amylin has been established in numerous studies. H... more The anorectic effect of the pancreatic peptide amylin has been established in numerous studies. Here, we investigated the influence of a pretreatment with dopamine (DA) D1- and D2-receptor antagonists on the anorectic effect of intraperitoneally injected amylin in rats fed a medium-fat (18% fat) diet. In 24-h food-deprived rats, pretreatment with the DA D2-receptor antagonist raclopride [100 μg/kg (0.2 μmol/kg) ip] significantly attenuated amylin's (5 μg/kg ip) anorectic effect, whereas raclopride alone had no effect on food intake [i.e., food intakes 1 h after injection were ( n = 12): NaCl/NaCl 7.3 ± 0.5 g; NaCl/amylin 3.9 ± 0.6; raclopride/NaCl 7.7 ± 0.7; raclopride/amylin 5.6 ± 0.7]. Pretreatment with another DA D2 receptor antagonist, sulpiride [50 mg/kg (154 μmol/kg) ip], similarly reduced amylin's satiety effect, whereas pretreatment with the DA D1-receptor antagonist SCH-23390 [10 μg/kg (0.03 μmol/kg) ip] did not influence amylin's effect. SCH-23390, however, com...
decreases meal size in rats. PHYSIOL BEHAV 58(6) 1197-1202, 1995.-Adult male rats were intraperit... more decreases meal size in rats. PHYSIOL BEHAV 58(6) 1197-1202, 1995.-Adult male rats were intraperitoneally (IP) injected with 1.0 pg/kg amylin at the beginning of the dark phase in 24 h food deprived or undeprived rats, and a computerized system measured feeding behavior. In food deprived rats, amylin reduced the size of the first postdeprivation meal without affecting intrameal feeding rate or the size or timing of subsequent meals. The same pattern was observed in undeprived rats, but amylin also increased the latency to the first postinjection meal. In a conditioned taste aversion test, IP amylin (1/xg/kg) injection just prior to rats' first access to a saccharine-flavored version of their maintenance diet, failed to affect their subsequent selection of that diet relative to the maintenance diet 2 d later. Finally, 2-min meal-contingent hepatic portal infusions of amylin (1-3.2 /zg/rat) during nocturnal spontaneous meals in undisturbed, ad lib fi~d rats reduced the meal size and meal duration, and increased the postprandial satiety ratio. Again, feeding rate and the size and duration of subsequent meals were not affected. These results suggest that amylin inhibits feeding by facilitating meal-ending satiety processes. Amylin Food intake Meal patterns Spontaneous feeding Rat Conditioned taste aversion Postprandial satiety
In monogastric species, a considerable portion of amino acid nitrogen is absorbed across the brus... more In monogastric species, a considerable portion of amino acid nitrogen is absorbed across the brush-border membrane of the small intestine as small peptides (e.g., tripeptides and dipeptides). In ruminants, however, this process is less clear. Therefore, we investigated the uptake of radioactively labeled glycylsarcosine as a model dipeptide across the intestinal brush-border membrane using brush-border membrane vesicles prepared from the bovine small intestine. Uphill transport of glycylsarcosine was energized by a transmembrane H+ gradient and was further stimulated by an electrical potential difference across the membrane. Transport mediated by a carrier contributes to total glycylsarcosine transport across the brush-border membrane. Comparison of the apparent kinetic constants between brush-border membranes prepared from the proximal jejunum or ileum revealed similar half-saturating substrate concentrations (1.28 and 0.93 mmol/L for proximal jejunum and ileum, respectively), but maximal transport rates appeared to be somewhat higher in the proximal small intestine (2.15 and 1.20 nmol/mg of protein per 3 s for proximal jejunum and ileum, respectively). Uptake of glycylsarcosine was strongly inhibited by other dipeptides, but the amino acids glycine and sarcosine did not affect transport. Inhibition of glycylsarcosine uptake by cephalexin indicated an affinity of the carrier for cephalosporin antibiotics. Transport of intact dipeptides across the brush-border membrane of the small intestine might be of physiological importance in ruminants because the microbial and dietary proteins resistant to rumen degradation are digested and absorbed in the small intestine.
Pflügers Archiv - European Journal of Physiology, 1981
The kinetics of [3H]hypoxanthine entry into lamb mid-jejunum were measured using 2-rain mucosal e... more The kinetics of [3H]hypoxanthine entry into lamb mid-jejunum were measured using 2-rain mucosal exposures. Mucosal hypoxanthine uptake occurred by a Na +-and energy-dependent saturable mechanism indicating that a carrier-mediated active transport process is involved. Inhibitory measurements indicate that hypoxanthine, adenosine, uracil and thymine compete for a common entry mechanism. Adenine, uric acid, allantoine and thymidine produced no significant inhibition of hypoxanthine entry. In additional experiments hypoxanthine was transported against a high concentration gradient from the mucosal to the serosal side of everted sacs of mid-jejunum. Therefore hypoxanthine appears to be absorbed by active transport from the lamb jejunum.
OBJECTIVE: Neurons in the area postremaanucleus of the solitary tract (APaNTS) region mediate amy... more OBJECTIVE: Neurons in the area postremaanucleus of the solitary tract (APaNTS) region mediate amylin's anorectic effect elicited by a single intraperitoneal (i.p.) injection of a low dose (5 mgakg). Here, we tested if a sustained elevation in amylin levels which was achieved by chronic amylin infusion reduces food intake by acting in the APaNTS region or, possibly, at other brain sites. Further, we tested the role of the APaNTS region in mediating the anorectic effects of high doses of amylin and its receptor agonist salmon calcitonin (sCT) after an acute single injection. DESIGN: Amylin (2 mgakgah) was chronically infused i.p. by osmotic minipumps in APaNTS-lesioned (AP-X) or sham-lesioned (SHAM) rats. For the acute experiments, amylin or sCT was injected i.p. at doses of 0.5 (only sCT), 5 or 50 mgakg. Food intake was measured by a computerized system. Body weight was assessed by manually weighing the rats. RESULTS: Amylin signi®cantly reduced cumulative food intake for about 7 days in SHAM but not in AP-X rats. Amylin's effect in SHAM rats was mainly due to a reduction of the size of nocturnal meals (eg average meal size during the ®rst four dark phases; SHAM, NaCl 4.1 AE 0.6 vs amylin 2.6 AE 0.4 g; n 6, P`0.05; AP-X, 2.6 AE 0.3 vs 3.7 AE 0.3) while light phase food intake was unaffected. Body weight gain over the whole 14 day infusion period was reduced by amylin in SHAM (NaCl 61 AE 6 vs amylin 46 AE 4 g; P`0.05) but not in AP-X rats (54 AE 4 vs 62 AE 4). After single injection, the anorectic effect of high doses of amylin and sCT (50 mgakg) was attenuated, but not abolished, in AP-X rats. CONCLUSION: We conclude that, under our experimental conditions, neurons in the APaNTS region are necessary for chronically elevated peripheral amylin to reduce food intake in rats. High doses of amylin, however, may be able to overrun these receptors and reduce feeding by acting at other brain sites.
Tricarballylic acid is a non-metabolizable rumen bacterial fermentation product of the naturally ... more Tricarballylic acid is a non-metabolizable rumen bacterial fermentation product of the naturally occurring tricarboxylic acid trans-aconitic acid. The aim of the present study was to investigate intestinal absorption of tricarballylate using brush-border membrane vesicles (BBMVs) isolated from the proximal jejunum of steers by a Ca2+ precipitation method with subsequent differential centrifugation. Transport of tricarballylate was investigated indirectly (influence of tricarballylate on the uptake of 14C-labelled citrate) as well as directly (uptake of 3H-labelled tricarballylate). Citrate as well as tricarballylate uptake (at a concentration of 0.05 mmol l-1) was strongly stimulated by an inwardly directed initial Na+ gradient. Furthermore, transport of both tricarboxylates under Na+ gradient conditions was clearly enhanced by lowering the extravesicular pH from 7.8 to 5.6. The imposition of an inwardly directed H+ gradient (pH(out)/pH(in) = 5.6/7.8) further enhanced the intravesicular accumulation of citrate as well as of tricarballylate compared with pH(out)/pH(in) = 5.6/5.6. Unequivocal evidence for a common transport site for tricarballylate and citrate was obtained from &#39;cis-inhibition&#39; and &#39;trans-stimulation&#39; of Na(+)-dependent citrate uptake by tricarballylate. In further experiments the influence of different substances on the uptake of 3H-labelled tricarballylate was evaluated. Unlabelled tricarballylate, citrate, succinate as well as trans- and cis-aconitate significantly inhibited the accumulation of 3H-labelled tricarballylate by BBMVs. Tricarballylate uptake as a function of the tricarballylate concentration revealed a Na(+)-dependent saturable component (apparent kinetic parameters: maximal transport capacity (Vmax) = 119 pmol (mg protein)-1 (3s)-1; affinity constant (Km) = 0.097 mmol l-1) and a Na(+)-independent diffusional component (diffusion constant: 169 nl (mg protein)-1 (3s)-1). It is concluded that tricarballylate and citrate are transported across the intestinal brush-border membrane by a common, Na(+)-dependent transport mechanism. The stimulatory influence of a low extravesicular pH most probably indicates that the protonated forms of tricarboxylates are better transported than the trivalent species.
Changes in food intake, body weight, and meal patterns brought about by repeated injections of in... more Changes in food intake, body weight, and meal patterns brought about by repeated injections of insulin were investigated. Male Sprague-Dawley albino rats were subcutaneously injected with slow-acting insulin twice daily for 3 days, 4 IU/injection on Day 1 and 6 IU/injection thereafter. Food intake and body weight were increased by the injections. Hyperphagia was most marked during the bright phase of the lighting cycle. Meal frequency increased during both lighting phases and nocturnal meal duration decreased, resulting in disappearance of the normal circadian rhythmicity of feeding. Postinsulin, food intake and body weight decreased. Body weight returned to control levels within 48 hr after insulin treatment, although the net hypophagia during this time failed to match the degree of the preceding hyperphagia. Postinsulin hypophagia, manifested primarily as a reduction in meal duration, was evident in both lighting phases. The data suggest that both behavioral and metabolic adaptations contribute to the renormalization of body weight following insulin treatments and that different controls of food intake operate during insulin hyperphagia and postinsulin hypophagia.
Mucosal uptake of succinate across the luminal epithelial border in various segments of the large... more Mucosal uptake of succinate across the luminal epithelial border in various segments of the large intestine of the rat (proximal and distal colon, caecum) was investigated using an in vitro mucosal uptake technique. For comparison, some experiments with jejunal preparations were also performed. Additionally, disappearance of succinate from the lumen of ligated loops of the proximal and distal colon was measured in vivo. In the ligated loop experiments, the succinate concentration of the instilled solution significantly decreased during a period of 30 min in both colonic segments, indicating absorption of succinate. The in vitro experiments revealed a distinct Na+ dependence of mucosal succinate uptake in all intestinal segments investigated. Because succinate uptake by the colonic mucosa of germ‐free rats was similarly enhanced in the presence of Na+ compared with Na(+)‐free conditions, measured uptake appears to be due to mucosal uptake rather than to Na(+)‐dependent uptake of succ...
data from our laboratory indicate that deeper, more mesial discharges may also be recorded neurom... more data from our laboratory indicate that deeper, more mesial discharges may also be recorded neuromagnetically. These results demonstrate that by neuromagnetic mapping of interictal spikes in the human brain it is possible to identify with precision the three-dimensional location of intracortical sources producing epileptiform discharges. Further analyses of the orientation, polarity, and timing of these fields, coupled with detailed postsurgical histological data, may provide insight about rapidly occurring cellular events underlying interictal spiking.
We tested whether pancreatic glucagon&#39;s effects on satiety and hepatic glycogenolysis dep... more We tested whether pancreatic glucagon&#39;s effects on satiety and hepatic glycogenolysis depend on variations in the macronutrient composition of the diet. Rats were kept on high carbohydrate, high fat, or high protein diets (HC-, HF- or HP-rats, respectively) and adapted to a 5 hour feeding (11:00-16:00)-19 hour deprivation (16:00-11:00) schedule. Glucagon (540 mcg/kg body weight) was intraperitoneally injected at 14:00. Glucagon stimulated similar amounts of hepatic glycogenolysis in HC- and in HF-rats and less glycogenolysis in HP-rats, but glucagon decreased food intake only in HC-rats. When HF- or HP-rats were prefed the HC-diet once for 1 hour (11:00-12:00) prior to injection, glucagon stimulated hepatic glycogenolysis similarly in both groups but decreased food intake only in HF-rats. Therefore, stimulation of hepatic glycogenolysis by glucagon is not sufficient to elicit satiety under all feeding conditions. The results also suggest that glucagon-induced satiety is not limited to carbohydrate intake.
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Papers by Erwin Scharrer