DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Table 8–2
Characteristics of Subtypes of Nicotinic Acetylcholine Receptors (nAChRs)
RECEPTOR
(Primary
MAIN
Receptor SYNAPTIC MEMBRANE MOLECULAR
Subtype) a LOCATION RESPONSE MECHANISM AGONISTS ANTAGONISTS
Skeletal Muscle Skeletal Excitatory; Increased cation ACh Atracurium
(N m
) (α 1
) 2
β 1
εδ neuromuscular end-plate permeability Nicotine Vecuronium
adult (α 1
) 2
β 1
γδ junction depolarization; (Na + ; K + ) Succinylcholine d-Tubocurarine
fetal (postjunctional) skeletal muscle Pancuronium
contraction
α-Conotoxin
α-Bungarotoxin
Peripheral Autonomic Excitatory; Increased cation ACh Trimethaphan
Neuronal (N n
) ganglia; depolarization; permeability Nicotine Mecamylamine
(α 3
) 2
(β 4
) 3
adrenal firing of (Na + ; K + ) Epibatidine
medulla postganglion Dimethylphenylneuron;
piperazinium
depolarization
and secretion of
catecholamines
Central Neuronal CNS; pre- and Pre- and post- Increased cation Cytosine, Mecamylamine
(CNS) postjunctional synaptic permeability epibatidine Dihydro-β-
(α 4
) 2
(β 4
) 3
excitation (Na + ; K + ) Anatoxin A erythrodine
(α-btox- Prejunctional Erysodine
insensitive) control of Lophotoxin
transmitter
release
(α 7
) 5
(α-btox- CNS; Pre- and Pre- and post- Increased Anatoxin A Methyllycaconitine
sensitive) post-synaptic synaptic permeability α-Bungarotoxin
excitation (Ca 2+ ) α-Conotoxin ImI
Prejunctional
control of
transmitter
release
a
Nine α (α 2
-α 10
) and three β (β 2
-β 4
) subunits have been identified and cloned in human brain, which combine in various conformations to form individual
receptor subtypes. The structure of individual receptors and the subtype composition are incompletely understood. Only a finite number of
naturally occurring functional nAChR constructs have been identified. α-btox, β-bungarotoxin.
and by G protein–induced changes in the function of
distinct member-bound effector molecules. The M 1,
M 3
,
and M 5
subtypes couple through the pertussis
toxin–insensitive G q/11
responsible for stimulation of
phospholipase C (PLC) activity. The immediate result
is hydrolysis of membrane phosphatidylinositol 4,5
diphosphate to form inositol polyphosphates. Inositol
trisphosphate (IP 3
) causes release of intracellular Ca 2+
from the endoplasmic reticulum, with activation of
Ca 2+ -dependent phenomena such as contraction of
smooth muscle and secretion (Chapter 3). The second
product of the PLC reaction, diacylglycerol, activates
PKC (in conjunction with Ca 2+ and phosphatidylserine).
This arm of the pathway plays a role in the phosphorylation
of numerous proteins, leading to various
physiological responses. Activation of M 1
, M 3
, and M 5
receptors can also cause the activation of phospholipase
A 2
, leading to the release of arachidonic acid and
consequent eicosanoid synthesis, resulting in
autocrine/paracrine stimulation of adenylyl cyclase and