title: M3-subtype muscarinic receptor that controls intracellular calcium release and inositol phosphate accumulation in gastric parietal cells.
abstract: The muscarinic receptor subtype which triggers acid secretion was investigated in isolated rabbit gastric parietal cells. Cytosolic free Ca2+ concentration ([Ca2+]i), measured with the fluorescent indicator FURA-2, increased rapidly after full agonist (carbachol) stimulation (6-8 sec), then returned to an intermediate sustained value. Other M2-agonists, oxotremorine and arecoline, produced a partial [Ca2+]i increase, whereas M1-agonists, pilocarpine and [4-m-chlorophenylcarbamoyloxyl]-2-butynyl-trimethylammonium, were without any significant effect. [Ca2+]i rise was inhibited by selective muscarinic antagonists: atropine greater than 4-diphenylacetoxy-N-methyl-piperidine methbromide greater than quinuclidinylbenzilate (QNB) greater than pirenzepine greater than 11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H- pyrido[2,3-b][1,4]benzodiazepine-6-one, this sequence being characteristic of the involvement of an M3-subtype. This inhibition was shown to be stereoselective; dexetimide and (-)QNB were more potent than levetimide and (+)QNB. The IC50 values for inhibition of [Ca2+]i increase by muscarinic antagonists were in good agreement with those obtained for inhibition of phospholipase C activation. In conclusion, the muscarinic receptor that controls acid secretion appears to be of the M3-subtype and the biochemical events coupled to the activation of this receptor system are also controlled through the same subtype.
authors.affiliation: Laboratoire de Biochimie des Membranes du CNRS UPR-8402-INSERM U-249, Faculté de Pharmacie, Montpellier, France.
authors.forename: A
authors.initials: A
authors.lastname: Leonard
authors.forename: P
authors.initials: P
authors.lastname: Cuq
authors.forename: R
authors.initials: R
authors.lastname: Magous
authors.forename: J P
authors.initials: JP
authors.lastname: Bali
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D018727:Muscarinic Antagonists; D010295:Parietal Cells, Gastric / Q000378:metabolism* / Q000648:ultrastructure; D010716:Phosphatidylinositols / Q000378:metabolism; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000502:physiology*
chemical_list: D007295:Inositol Phosphates; D018727:Muscarinic Antagonists; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D002217:Carbachol; D000109:Acetylcholine; D002118:Calcium