Türk Biyokimya Dergisi (Sep 2006)
Distribution of Muscarinic Acethylcholine Receptors and Related Signal
Abstract
Muscarinic receptors are members of G protein coupled receptor family. Molecularcloning studies indicate five intronless genes that encode five muscarinic receptorglycoproteins. Muscarinic receptor genes are fairly similar between species.Muscarinic receptors mediate many cellular responses by activating second messengersystems through the action of G proteins. Muscarinic receptors are divided into twofunctional categories; M1, M3, and M5 receptors preferentially couple to the Gq/11protein which activates phospholipase C, whereas M2 and M4 receptors preferentiallycouple to Gi/o protein, which inhibits adenylate cyclase activity. Muscarinic receptorsare distributed widely in central and peripheral tissues. M1 receptors are found in theforebrain, especially in the hippocampus and cerebral cortex. M2 receptors are foundheart and brainstem, M3 receptors are found in the smooth muscle, exocrine glandsand cerebral cortex. M4 receptors are seen in the neo-striatum and M5 receptor mRNAis found in the substantia nigra. M2 receptors in the CNS are the main muscarinicacethylcholine receptors that mediate acethylcholine induced MAP kinase activationwhich is necessary for memory. The brain M2 receptors play important role forantinociception. In addition, M2 receptors are essential for muscarinic acethylcholinereceptor-dependent bradycardia and agonist induced contraction of stomach, urinarybladder and trachea. M3 receptors are involved in salivary secretion, pupillaryconstriction and bladder detrusor contraction. Brain M4 receptors are participate inthe modulation of central dopaminergic responses and regulate peripheral smoothmuscle tone. M5 receptors may regulate dopamine release. But this regulation isnot fully understood. Muscarinic receptors are involved in different pathologicalconditions such as heart failure, Alzheimer disease and asthma. Identification ofmuscarinic receptor subtypes expressed in various cells and tissues is important inthe de-velopment of selective drugs.
