Muscarinic acetylcholine receptor family (mAChR)

The muscarinic acetylcholine receptor family (mAChRs) comprises five distinct G protein-coupled receptor subtypes, M1 through M5, which mediate the metabotropic actions of acetylcholine [1]. These receptors are widely distributed across the central and peripheral nervous systems, where they regulate essential physiological functions [2]. Subtypes M1, M3, and M5 typically couple to Gq/11 proteins to stimulate phospholipase C, while M2 and M4 couple to Gi/o proteins to inhibit adenylyl cyclase [3]. In the periphery, they control heart rate, smooth muscle tone in the airways and bladder, and glandular secretions [4]. In the brain, mAChRs are vital for cognitive processes, including memory, attention, and motor control [5]. Dysregulation of these receptors is linked to several major diseases, such as Alzheimer's disease, schizophrenia, and chronic obstructive pulmonary disease (COPD) [6]. Pharmacological agents targeting mAChRs include agonists like pilocarpine for glaucoma and antagonists like tiotropium for respiratory distress [7]. A primary hurdle in therapeutic development is the high sequence homology among subtypes, which makes achieving high selectivity difficult and often leads to side effects like dry mouth or tachycardia [8]. Sources: [1] UniProt (P11229, P08172, P20309, P08173, P08912); [2] PubMed (PMID: 9647868); [3] StatPearls (Cholinergic Receptors); [4] Wikipedia (Muscarinic acetylcholine receptor); [5] NIH (NCBI Gene: CHRM1); [6] PubMed (PMID: 15128298); [7] PubChem (Atropine, Pilocarpine); [8] PubMed (PMID: 16432316).

Other names

Muscarinic receptorsMuscarinic cholinergic receptorsCHRM1-5M1-M5 receptorsMuscarinic acetylcholine receptors

Drugs targeting the muscarinic receptor family act as either agonists, which mimic acetylcholine to activate G protein signaling (Gq for M1/M3/M5 or Gi/o for M2/M4), or antagonists, which competitively inhibit acetylcholine binding to prevent receptor activation.