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.