Various pharmacologic and molecular biology studies have identified at least two
distinct types of nicotinic cholinergic receptors (cholinoceptors). The NNreceptor is
found in postganglionic neurons and in some presynaptic cholinergic terminals; the NM
receptor is found in skeletal muscle, at the neuromuscular endplate. Ligand binding
to either of these receptors leads to opening of Na+and K+channels with subsequent
cellular depolarization. These two receptors have differing structural features in terms
of their subunit construction. The NMreceptor has a pentameric structure consisting of
α,β,γ, and δ units; the NNreceptor has α andβ subunits only.
4.2.3 The Muscarinic Acetylcholine ReceptorEven though the muscarinic receptor, which is present in postganglionic parasympa-
thetic synapses, is much more stereospecific and structure-specific than its nicotinic
counterpart, only since the 1980s have any molecular studies been undertaken to
explore similarities and differences between the two classes of AChR. It has been
labeled with the affinity label [^3 H] propyl-benzilylcholine-mustard (4.5).
Muscarinic receptors may be classified into subtypes based upon their molecular
structure, signal transduction properties, and various ligand affinities. To date, three
types have been identified: M 1 ,M 2 , and M 3. All three subtypes are present in the cen-
tral nervous system, subserving functions such as memory, learning, pain perception,
and cortical excitability. The correlation of specific mentation processes to particular
receptor subtypes has not yet been achieved. Elsewhere, these three receptor subtypes
participate in various processes. M 1 receptors are present on nerve cells where they
facilitate impulse transmission from preganglionic axon terminals to ganglion cells. M 2
receptors mediate acetylcholine effects on the heart; these receptors open K−channels
in cardiac tissue, affecting sinoatrial pacemaker cells and thus slowing heart rate.
M 3 receptors regulate smooth muscle tone in the gastrointestinal tract and in bronchi,
causing stimulation of phospholipase C and increase in muscle tone. By an analogous
mechanism, M 3 receptors in various glands mediate increased glandular secretion. In
blood vessels, the relaxant action of ACh on muscle tone is indirectly mediated via M 3
receptors that facilitate the release of nitric oxide.
4.2.4 Cholinergic Receptor AgonistsIncreased stimulation of the AChR can be achieved in two ways: (1) by binding of the
directly acting cholinergic agonists to the AChR, triggering nicotinic or muscarinic
NEUROTRANSMITTERS AND THEIR RECEPTORS 209