Marmara Üniversitesi Tıp Fakültesi Biyofizik A.B.D

Muscarinic receptors are members of G protein coupled receptor family. Molecular cloning studies indicate five intronless genes that encode five muscarinic receptor glycoproteins. Muscarinic receptor genes are fairly similar between species. Muscarinic receptors mediate many cellular responses by activating second messenger systems through the action of G proteins. Muscarinic receptors are divided into two functional categories; M₁, M₃, and M₅ receptors preferentially couple to the Gq/11 protein which activates phospholipase C, whereas M₂ and M₄ receptors preferentially couple to Gi/o protein, which inhibits adenylate cyclase activity. Muscarinic receptors are distributed widely in central and peripheral tissues. M₁ receptors are found in the forebrain, especially in the hippocampus and cerebral cortex. M₂ receptors are found heart and brainstem, M₃ receptors are found in the smooth muscle, exocrine glands and cerebral cortex. M₄ receptors are seen in the neo-striatum and M₅ receptor mRNA is found in the substantia nigra. M₂ receptors in the CNS are the main muscarinic acethylcholine receptors that mediate acethylcholine induced MAP kinase activation which is necessary for memory. The brain M₂ receptors play important role for antinociception. In addition, M₂ receptors are essential for muscarinic acethylcholine receptor-dependent bradycardia and agonist induced contraction of stomach, urinary bladder and trachea. M₃ receptors are involved in salivary secretion, pupillary constriction and bladder detrusor contraction. Brain M₄ receptors are participate in the modulation of central dopaminergic responses and regulate peripheral smooth muscle tone. M₅ receptors may regulate dopamine release. But this regulation is not fully understood. Muscarinic receptors are involved in different pathological conditions such as heart failure, Alzheimer disease and asthma. Identification of muscarinic receptor subtypes expressed in various cells and tissues is important in the development of selective drugs.