title: Role of calcium and calmodulin in activation of the oxyntic cell by histamine and carbamylcholine in the guinea pig.
abstract: The role of calcium in stimulation of the oxyntic cell by histamine and carbamylcholine was studied using a sensitive quantitative cytochemical staining technique that measures oxyntic cell hydroxyl ion production (HIP) as an index of acid secretion. Histamine (10(-17)-10(-14) M), carbamylcholine (10(-12)-10(-9) M), and extracellular calcium (10(-7)-10(-3) M) caused a linear, dose-dependent stimulation of the oxyntic cell. EGTA (10(-6) M) inhibited carbamylcholine by 50% but not histamine-stimulated activity. Lanthanum chloride (10(-6) M) caused 100% inhibition of carbamylcholine-induced activity but did not affect histamine-stimulated activity. A maximally effective dose of calcium (10(-4) M) caused additive effects on HIP at low doses of carbamylcholine without alteration of the maximal effect of carbamylcholine. Calcium (10(-4) M) did not enhance the effects of histamine. The calmodulin antagonists, trifluoperazine (10(-5) M), pimozide (10(-5) M), and a naphthalenesulfonamide (W-7), inhibited the integrated response to histamine by 54, 56, and 53%, and that of carbamylcholine by 65, 64, and 99%, respectively. Thus, extracellular calcium per se, stimulates the oxyntic cell. The action of carbamylcholine is completely dependent upon calcium/calmodulin mediation, supporting the concept that cholinergic actions are mediated via calcium-calmodulin events. Although histamine does not require extracellular or membrane calcium events to stimulate the oxyntic cell, calmodulin appears to participate in histamine action.
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000187:drug effects; D010868:Pimozide / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
chemical_list: D002135:Calcium-Binding Proteins; D002147:Calmodulin; D007473:Ion Channels; D013449:Sulfonamides; D010868:Pimozide; D014268:Trifluoperazine; C017967:W 7; D006632:Histamine; D002217:Carbachol; D002118:Calcium