Muscarinic acetylcholine receptor
They play several roles, including acting as the main end-receptor stimulated by acetylcholine released from postganglionic fibers.Many drugs and other substances (for example pilocarpine and scopolamine) manipulate these two distinct receptors by acting as selective agonists or antagonists.The chromaffin cells of the adrenal medulla act as "modified neurons", releasing adrenaline and noradrenaline into the bloodstream as hormones instead of as neurotransmitters.Another role for these receptors is at the junction of the innervated tissues and the postganglionic neurons in the parasympathetic division of the autonomic nervous system.The sympathetic nervous system also has some preganglionic nerves terminating at the chromaffin cells in the adrenal medulla, which secrete epinephrine and norepinephrine into the bloodstream.Muscarinic acetylcholine receptors are also present and distributed throughout the local nervous system, in post-synaptic and pre-synaptic positions.By the use of selective radioactively labeled agonist and antagonist substances, five subtypes of muscarinic receptors have been determined, named M1–M5 (using an upper case M and subscript number).[citation needed] Meanwhile, geneticists and molecular biologists have characterised five genes that appear to encode muscarinic receptors, named m1-m5 (lowercase m; no subscript number).[27] This receptor is found mediating slow EPSP at the ganglion in the postganglionic nerve,[28] is common in exocrine glands and in the CNS.[29][30] It is predominantly found bound to G proteins of class Gq,[31] which use upregulation of phospholipase C and, therefore, inositol trisphosphate and intracellular calcium as a signaling pathway.Because the M3 receptor is Gq-coupled and mediates an increase in intracellular calcium, it typically causes contraction of smooth muscle, such as that observed during bronchoconstriction and bladder voiding.[36] In early clinical trials of moderate to high severity patients without treatment resistant history, it has demonstrated efficacy about equivalent to that of other anti-psychotics (20-point improvement in PANSS vs 10-point placebo improvement), with a notably different side effect profile (very low rates of metabolic effects, hypotension, weight changes, or EPS) with moderately reported rates of nausea and constipation.
AcetylcholinenicotinicMuscarineAtropineacetylcholine receptorsG protein-coupled receptor complexescell membranesneuronspostganglionic fibersparasympathetic nervous systemsympathetic nervous systemsweat glandsnicotinenicotinic acetylcholine receptorsautonomic nervous systempilocarpinescopolamineagonistsantagonistsAcetylcholine (ACh)neurotransmitterneuromuscular junctionsautonomic gangliaautonomic ganglionadrenal medullachromaffin cellsepinephrinenorepinephrinesomatic nervous systempostsynapticmetabotropic receptorsG proteinsligandreceptorseven transmembrane regionsligand-gated ion channelion channelGq proteinspirenzepinegeneticistsmolecular biologistsbioinformaticG-proteinscholera toxinpertussis toxinlong-term potentiationlearningspatial memoryarecolineoxotremorinecarbachol77-LH-28-1NebracetamDesmethylclozapineHyoscyamineDiphenhydramineDimenhydrinatetrospium chloridedicycloverinetolterodineoxybutyninipratropiummamba toxintelenzepinechlorpromazineheart ratecontractile forcesatriumconduction velocityAV nodehomotropic inhibitionmethacholinemethoctraminetripitraminegallaminebronchoconstrictionendocrineexocrine glandsalivary glandsstomachgastrointestinal motilityEye accommodationmiosismydriasisIris sphincter musclecerebral vascularvasodilationsystemic vascularemesisbethanecholdarifenacintiotropiumlocomotionprogenitor cellmyelodysplastic syndromeanemiasectivitiesMuscarinic acetylcholine receptor M1exocrine glandsphospholipaseinositol trisphosphateMuscarinic acetylcholine receptor M2sinus rhythmdepolarizationatrialcardiac muscleatrioventricular nodeventricularMuscarinic acetylcholine receptor M3bladder voidingnitric oxidewhich diffuses to adjacent vascular smooth muscle cells and causes their relaxationparasympathomimeticsphospholipase CMuscarinic acetylcholine receptor M4erythropoietinbronchospasmmuscarinic agonistsMuscarinic acetylcholine receptor M5LigandsParkinson's diseasemotion sicknessUnited States FDAxanomelinetrospiumMuscarinic agonist