MUSCARINIC ACETYLCHOLINE-RECEPTOR SUBTYPES IN SMOOTH-MUSCLE

Muscarinic acetylcholine M(2) and M(3) receptor subtypes are coexpressed in many types of smooth muscle including gastrointestinal smooth muscle, urinary bladder and vascular and airway tissue. Activation of M(3) receptors, via the G protein G(q), results in increased polyphosphoinositide hydrolysis, release of Ca2+ ions from the sarcoplasmic reticulum and consequently causes contraction. Quantitation of the relative expression of M(2) and M(3) receptors has shown that the proportion of M(2) receptors often predominates over the M(3) receptor population by 4:1 or more. Although it is established that M(2) receptors preferentially link, via a pertussis-toxin-sensitive G protein G(i), to inhibition of adenylate cyclase activity, relatively little is known concerning the physiological role of the M(2) receptor population. In this review, Richard Eglen and colleagues discuss recent data concerning the possible role(s) of muscarinic receptor subtypes in smooth muscle and appraise the pharmacological methods for dissecting the function of muscarinic receptor subtypes in tissues coexpressing multiple receptors.