http://www.bristol.ac.

uk/phys‐pharm/media/teaching/ Fundamental role of chemical communication

Mechanisms by which chemical

messengers control cells

Main text: V&L textbook, chapter 5,

Consistent with Germann chapter 5
Advanced: Cooper “The Cell”, Lodish et al “Mol. Cell Biology

Intercellular communication by chemical signals The most important step in inter-cellular communication:
1. Synaptic (nerve cells) 2. Endocrine Interaction (binding) of the chemical messenger molecule
to a specialised protein, the RECEPTOR.
a) Movement of
Endocrine
electric charge
gland
axon

along the Specialised proteins

nerve
1 which recognize signalling
molecules and trigger
Hormone
b) Release of a Target cellular responses
neurotransmitter cell
into synaptic cleft
NOT TO BE CONFUSED
Target
cell WITH:
c) Response of a Target Specialised nerve cells
postsynaptic cell cell 2 (detectors) which sense for
example temperature, pressure
etc and participate in various
3. Paracrine: diffusion of a reflexes
chemical signal in interstitial fluid to
the neighbour cells

Receptor What can activation of a receptor lead to?

 Change properties of the cell membrane, such as

its permeability to ions, water or its electrical
Ligand potential
 Change cellular metabolism (for example adrenalin
increases the rate at which many cells consume
glucose)
 Change in the rate of cell division and
differentiation (special “sex steroid hormones”
1. Chemical messenger physically interacts with a affect numerous cell types in the body to develop
special protein male or female appearance)
 Change in the cell’s (contractile) activity (adrenalin
2. This changes the shape (conformation) of this
increases the force of contractions of the heart)
protein to turn it into the “active” state
3. Activated protein (receptor) changes the cell’s
function

1
 Receptors are found: Intracellular receptors may be located as free-floating
proteins in the cytoplasm or nucleus
Inside the cell Cell surface
(in the cytoplasm or nucleus)

DNA

GENE expression
CHANGE
of cell Protein
function Synthesis

SYNOPSIS: Some signalling molecules cannot cross the

Intracellular receptors for signalling cell membrane.
molecules which can pass through the
membrane:
1 These are special proteins located in the nucleus or cytoplasm.
2 When activated these receptors bind to DNA and via
activation of specific genes lead to production of specific
proteins.
3 These proteins change some of the cell’s functions, for
example make it divide or secrete some chemicals or contract
stronger etc.
4. Important examples of intracellular receptors (more detail in
later lectures): thyroid hormone receptors and steroid
hormone receptors.
In addition:
Nitric oxide – a gaseous signalling molecule, crosses
cellular membranes. Has a different intracellular
signalling mechanism: its receptor is an enzyme.

Receptors for these signalling molecules

are located at the cell membrane

RECEPTORS of this kind are

characteristic of many SMs, for
example acetylcholine (used by many
nerve cells) or adrenalin (a hormone)
From “The Cell: A molecular Approach” G. Cooper

2
 3 main types of receptors found on cell membranes:
3 main types of receptors
found on cell membranes
1. Receptors which themselves are ion channels
(ligand-gated ion channels)

Nerve cells, muscle cells –

(e.g. EXCITABLE cells which have membrane
potential)

The acetylcholine receptor at the skeletal

muscle is an ion channel which opens when SYNOPSIS:
acetylcholine binds to it
+_ +
+_ _+
_ +
 In the absence of the signalling molecule (in this
+_ _
example acetylcholine) this ion channel is closed
Na+
+
Na+
+ _
_

 Binding of acetylcholine changes its shape

_ +
+ _
_

(conformation) so that it can pass numerous sodium

+
+ _ _
_ -70 mV _ +
ions
+ _ _
+ +
+ +

 Ions moving through the channel change

out potential of the cell’s membrane (in this example
+
in +_
+_ + _+
+
to more positive values)
 Change in membrane potential can:
_

Na+ Na+
_ + +

- trigger cell contraction (in muscle cells)

_ +
+ _
+
- make a nerve cell generate action potentials
+_
+
+10 mV _
+ + _ +
+
+

Membrane potential becomes more positive

(depolarisation occurs)

3 main types of receptors found on cell membranes:

2. Receptors which are enzymes or are

directly bound to enzymes

PHOSPHORYLATION

PROTEIN KINASES H2PO4-

KINASE

3
 In most cases there are several
1st reactions which follow each
other
2nd

Target protein must have a

Changes in
“consensus sequence” – a cell’s proteins
particular pattern of amino-acids
recognised by the enzyme !!!
Cell response
Other points to note:
Ligands for these receptors are often large molecules (e.g. insulin), this seems to
make it difficult to mimic the features of such ligands with small molecules which
are used as drugs.

3 main types of receptors found on cell membranes: A G-protein-coupled receptor may modulate
an ion channel directly via a G-protein
3. Receptors which act via G-proteins Hormone
Ions
Ionic channel
Receptor
G-proteins (from GTP-binding proteins):
G G
Small proteins consisting of 3 subunits:
α –subunit, β and Ƴ‐subunit G protein
Because β and Ƴ‐subunits never separate one can think
of G‐proteins as consisting of two parts:
α –subunit and βƳ‐subunit

Both, α and βγ subunits are used as signalling

intermediates in different situations.

A G-protein-coupled receptor may activate

an enzyme (such as adenylyl cyclase) SYNOPSIS:
Receptors which are coupled via G-proteins
Hormone Adenylyl cyclase (for example adrenalin receptors)

Receptor When activated, these receptors make G-proteins fall into two
parts which diffuse away from the receptor.

G G Activated G-proteins bind to other proteins and change their

Binds to function. This may lead to activation of some enzymes (for
example to mobilise glucose from its storage form glycogen) or
G protein many modulate ion channels (this will change membrane potential).
ATP cAMP proteins
and Most of the ligands for these receptors are small
changes molecules, for example acetylcholine, this makes the
GPCRs very “druggable” – e.g. good drug targets. Up to
their 40% of the currently used drugs act via GPCR pathways.
function

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 WHY DO THE CELLS NEED all THESE
COMPLICATED SIGNALLING PATHWAYS?

Type 2
Principle of amplification Type 1

A single activated receptor

SM triggers production of many Type 2
second-order messenger molecules
which in turn activate numerous Type 3
effector proteins

Figure 5.5 from Vander’s textbook

SUMMARY Features of binding of SM to the receptors:

Located intracellularly Located at cell membrane specificity

Receptors which operate Receptors which themselves

via gene expression are ion channels (“A”)
Receptors which act as
enzymes (for example, the SPECIFICITY of RECEPTORS is NOT
insulin receptor), (“B & C”) ABSOLUTE
Receptors which are
coupled via G-proteins (for
example adrenalin Acetylcholine (ACh) Noradrenaline (NA)
receptors) (“D”) CH3 HO
O
H
+
H3C-C-O CH2 CH2 N CH3 HO C CH NH
2 H
OH
CH3

Features of binding: saturation Features of binding: competitive nature

Saturation means that the If several molecules can bind

maximal effect of any SM to the same receptor they
will be limited by the number will compete and try to
of available receptors displace each other.
This principle underlies
mechanism of action of many
drugs which interfere with
SMs of the body and prevent
SMs from interacting with
their receptors.

5
Signalling What it may be called “Flavour” of the term
The key points:
molecule
1. Fundamentally, cells communicate using CHEMICAL MESSENGERS
(SM) Ligand Signifies the ability of the SM to 2. Ways of inter-cellular communication: paracrine, synaptic and
physically bind (“stick”) to the endocrine
receptor 2. Chemical messengers bind to specialised proteins, the RECEPTORS
3. Receptors are found: a) In the cytoplasm of the cell b) On the cell
surface
Agonist (of a particular Signifies the ability of SM to 4. Intracellular receptors usually work via a change in gene expression
receptor) activate the receptor 5. Cell membrane receptors come in 3 flavours:
a) Receptor- ion channels (ACh receptors in skeletal muscle)
Transmitter, Usually applied to the SMs b) Receptor-enzymes which usually phosphorylate other proteins
neurotransmitter released by nerve cells in synapses (insulin receptor)
c) Receptors which are coupled to G-proteins (adrenaline
receptors)
Hormone SM which is released from cells 6. Receptors-enzymes and GPCRs amplify the initial signal using second-
remote from the target and travels and third order intermediates
with blood 7. Features of ligand – to – receptor interaction: specificity,
saturation and competitive nature

COMMINICATE!

END