Protein Domain : Muscarinic acetylcholine receptor M4 IPR001432

Type	Family
Description	Muscarinic acetylcholine receptors are members of rhodopsin-like G-protein coupled receptor family. They play several important roles; they mediate many of the effects of acetylcholine in the central and peripheral nervous system and modulate a variety of physiological functions, such as airway, eye and intestinal smooth muscle contraction, heart rate and glandular secretions. The receptors have a widespread tissue distribution and are a major drug target in human disease. They may be effective therapeutic targets in Alzheimer's disease, schizophrenia, Parkinson's disease and chronic obstructive pulmonary disease [ , ]. There are five muscarinic acetylcholine receptor subtypes, designated M1-5 [ , , , , ]. The family can be further divided into two broad groups based on their primary coupling to G-proteins. M2 and M4 receptors couple to the pertussis-toxin sensitive Gi proteins, whereas M1, M3 and M5 receptors couple to Gq proteins [, ], which activate phospholipase C. The different subtypes can also couple to a wide range of diverse signalling pathways, some of which are G protein-independent [, , ].All subtypes seem to serve as autoreceptors [ ], and knockout mice reveal the important neuromodulatory role played by this receptor family [, , ].The muscarinic acetylcholine M4 receptor is primarily found in the CNS [ , , ], its distribution largely overlapping with that of M1 and M3 subtypes. M4 receptors function as inhibitory autoreceptors for acetylcholine [, ], activation of which inhibits acetylcholine release in the striatum.Muscarinic acetylcholine receptors possess a regulatory effect on dopaminergic neurotransmission and activation of M4 receptors in the striatum inhibits dopamine-induced locomotor stimulation in mice [ ]. M4 receptor-deficient mice exhibit increased locomotor simulation in response to dopamine agonists, such as amphetamine and cocaine [, , , ]. Neurotransmission in the striatum influences extrapyramidal motor control. Therefore, alterations in M4 receptor activity may contribute to conditions such as Parkinson's Disease [, , ].
Short Name	Musac_Ach_M4_rcpt