The Interaction of Histamine with Gastrin and Carbamylcholine on Oxygen Uptake by Isolated Mammalian Parietal Cells

Abstract

Using oxygen uptake as an index of the physiological response of isolated parietal cells, the interactions between histamine and gastrin and between histamine and carbamylcholine and the effects of atropine and metiamide on these interactions have been studied. Parietal cells were isolated from canine fundic mucosa by sequential exposure of separated mucosa to collagenase and EDTA. In previous studies carbamylcholine, isobutyl methyl xanthine, gastrin, and histamine have each been shown to increase oxygen uptake by these cells. Isobutyl methyl xanthine greatly enhanced the histamine effect. Carbamylcholine was inhibited by atropine but not by metiamide, histamine was inhibited by metiamide but not by atropine, and gastrin was inhibited by neither, suggesting that each of these agents has a direct action on the parietal cell. In the present studies, potentiating interactions between histamine and carbamylcholine and between histamine and gastrin have been demonstrated. Against a histamine (0.1 and 1 muM) plus isobutyl methyl xanthine (0.1 mM) background, the dose for 50% response for gastrin was approximately 1 nM, and the maximal response was obtained at 0.1 muM. When added to these combinations of stimulants, metiamide and atropine retained their respective specificities against stimulation by histamine and carbamylcholine, in that responses were inhibited to the level that was seen when the component of the pair that was not inhibited was given alone. The observation that histamine plus gastrin and histamine plus carbamylcholine produced maximal responses that were greater than the maximal response to histamine alone further supports the hypothesis that these agents each have direct actions on parietal cells. These observations are not consistent with the hypothesis that histamine is the sole mediator for the effects of other secretagogues. Furthermore, the inhibitory effects of atropine and metiamide on the specific cholinergic and histaminic components of the interactions that occur between secretagogues provide a possible explanation for the apparent lack of specificity of these agents on in vivo acid secretion.