Effect of glucagon on adenylate cyclase activity and acid production of isolated human parietal cells.

The direct effect of glucagon on human parietal cell function in vitro was tested by measuring adenylate cyclase (AC) activity and H+ production in homogenates of human gastric mucosa obtained during surgery or at biopsy. Cells isolated from mucosa obtained during surgery showed an increase in AC with histamine and glucagon. In parietal cell enriched fractions (75%) glucagon and histamine stimulated AC much more effectively than in parietal cell depleted fractions (15% and 7%). In contrast, glucagon did not affect basal or histamine stimulated 14C amino pyrine uptake. In homogenates of mucosal biopsy specimens 2 X 10(-7) mol/l glucagon enhanced AC activity by 76% (corpus) and 20% (antrum). In the same homogenates 10(-4) mol/l histamine caused a stimulation by 161% (corpus) and 38% (antrum). In fundic biopsy specimens glucagon displayed a biphasic concentration response curve with an increase at 10(-10) mol/l (46% above basal AC activity) and a maximum at 2 X 10(-7) mol/l (97%). Histamine elicited the maximal response (192%) at 10(-3) mol/l. Increasing histamine and glucagon concentrations caused additive stimulation of AC. Ranitidine did not change AC in response to glucagon but abolished the effect of histamine. Data suggest that the glucagon action is mediated by separate (glucagon?) receptors. As H+ production was not affected by glucagon, the coexistence of two AC systems in the human parietal cell is postulated: One that is activated via histamine H2-receptors and which stimulated H+ production; another that is activated by glucagon and is directed towards other, possibly metabolic effects.