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

Table 8–3
Characteristics of Muscarinic Acetylcholine Receptor Subtypes (mAChRs) (continued)
SIZE; CELLULAR AND CELLULAR FUNCTIONAL DISEASE
RECEPTOR CHROMOSOME TISSUE LOCATION a RESPONSE b RESPONSE c RELEVANCE
M 1
460 aa CNS; Most abundant Couples by G q/11
Increased cognitive Alzheimer’s disease
llq 12-13 in cerebral cortex, Activation of PLC; function (learning Cognitive
hippocampus, ↑ IP 3
and ↑ DAG → and memory) dysfunction
striatum and ↑ Ca 2+ and PKC Increased seizure Schizophrenia
thalamus Depolarization and activity
Autonomic ganglia excitation Decrease in dopamine
Glands (gastric and (↑ sEPSP) release and
salivary) Activation of locomotion
Enteric nerves PLD 2
, PLA 2
; Increase in
↑ AA
depolarization
of autonomic
ganglia
Increase in
secretions
M 2
466 aa Widely expressed in Couples by G i
/G o
Heart: Alzheimer’s disease
7q 35-36 CNS, hind brain, (PTX-sensitive) SA node: slowed Cognitive
thalamus, cerebral Inhibition of spontaneous dysfunction
cortex, hippocampus, AC, ↓ cAMP depolarization; Pain
striatum, heart, Activation of hyperpolarization,
smooth muscle, inwardly rectifying ↓ HR
autonomic nerve K + channels AV node: decrease in
terminals Inhibition of voltage- conduction velocity
gated Ca 2+ channels
Hyperpolarization
and inhibition
Atrium: ↓ refractory
period, ↓ contraction
Ventricle: slight
↓ contraction
Smooth muscle:
↑ Contraction
Peripheral nerves:
Neural inhibition
via autoreceptors
and heteroreceptor
↓ Ganglionic
transmission.
CNS:
Neural inhibition
↑ Tremors;
hypothermia;
analgesia
(Continued)
an increase in cyclic AMP. These effects of M 1
, M 3
, and
M 5
mAChRs are generally secondary to elevations of
intracellular Ca ++ (Eglen, 2005).
Stimulation of M 2
and M 4
cholinergic receptors
leads to interaction with other G proteins, (e.g., G i
and G o
)
with a resulting inhibition of adenylyl cyclase, leading
to a decrease in cyclic AMP, activation of inwardly rectifying
K + channels, and inhibition of voltage-gated Ca 2+
channels (van Koppen and Kaiser, 2003). The functional
consequences of these effects are hyperpolarization