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Receptor Types

Receptors are macromolecules that operate to bind mediator substances and transducer

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this binding into an effect, i. e., a change in cell function. Receptors differ in terms
of their structure and the manner in which they translate occupancy by a ligand into a
cellular response (signal transduction).

G-Protein coupled receptors (A) consist of an amino acid chain that weaves in and out of
the membrane in serpentine fashion. The extramembranal loop regions of the molecule
may possess sugar residues at different N-glycosylation sites. The seven α- helical
membrane-spanning domains probably form a circle around a central pocket that carries
the attachment sites for the mediator substance. Binding of the mediator molecule or of a
structurally related agonist molecule induces a change in the conformation of the receptor
protein, enabling the latter to interact with a G-protein (= guanyl nucleotide-binding
protein). G-proteins lie at the inner leaf of the plasmalemma and consist of three subunits
designated α, β, and γ. There are various G-proteins that differ mainly with regard to their
α-unit. Association with the receptor activates the G-protein, leading in turn to activation
of another protein (enzyme, ion channel). A large number of mediator substances act via
G-protein-coupled receptors (see p. 66 for more details).

An example of a ligand-gated ion channel (B) is the nicotinic cholinoceptor of the motor
end plate. The receptor complex consists of five subunits, each of which contains four
transmembrane domains. Simultaneous binding of two acetylcholine (ACh) molecules
to the two α-subunits results in opening of the ion channel with entry of Na+ (and exit of
some K+), membrane depolarization, and triggering of an action potential.

The neuronal N-cholinoceptors apparently consist only of α- and β-subunits. Some of

the receptors for the transmitter γ-aminobutyric acid (GABA) belong to this receptor
family: the GABAA subtype is linked to a chloride channel (and also to a benzodiazepine
binding site,). Glutamate and glycine both act via ligand-gated ion channels.

The insulin receptor protein represents a ligand-operated enzyme (C), a catalytic receptor.
When insulin binds to the extracellular attachment site, a tyrosine kinase activity
is “switched on” at the intracellular portion. Protein phosphorylation leads to altered cell
function via the assembly of other signal proteins. Receptors for growth hormones also
belong to the catalytic receptor class.

Protein synthesis regulating receptors (D) for steroids and thyroid hormone are found
in the cytosol and in the cell nucleus, respectively. The receptor proteins are located
intracellularly; depending on the hormone, either in the cytosol (e. g., glucocorticoids,
mineralocorticoids, androgens, and gestagens) or in the cell nucleus (e. g., estrogens,
thyroid hormone). Binding of hormone exposes a normally hidden domain of the receptor
protein, thereby permitting the latter to bind to a particular DNA nucleotide sequence
on a gene and to regulate its transcription. The ligand–receptor complexes thus function
as transcription regulating factors. Transcription is usually initiated or enhanced, rarely
blocked.

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The hormone–receptor complexes interact pairwise with DNA. These pairs (dimers)
may consist of two identical hormone–receptor complexes (homodimeric form, e. g.,
with adrenal or gonadal hormones). The thyroid hormone–receptor complex occurs in
heterodimeric form and combines with acid-retinoic acid-receptor complex.

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