Drug-Receptor Interaction VI

Receptor Types
Receptors are macromolecules that bind
mediator substances and transduce 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
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 Nglycosylation
sites. The seven !-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 .
There are various G-proteins that differ
mainly with regard to their !-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.
An example of a ligand-gated ion
channel is the nicotinic cholinoceptor
of the motor endplate. The receptor
complex consists of five subunits, each
of which contains four transmembrane
domains. Simultaneous binding of two
acetylcholine (ACh) molecules to the
two !-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 ganglionic N-cholinoceptors
apparently consist only of ! and " subunits
. Some of the receptors for
the transmitter #-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 ligandgated
ion channels.