Effects of glucagon and histamine on human parietal cells.
Since in vivo pancreatic glucagon inhibits gastric acid secretion it was of interest to test its direct effect on human parietal cell function in vitro by measuring adenylate cyclase (AC) activity and H+ production. Cells were isolated from human gastric mucosa obtained at surgery for peptic ulcer. In enriched (75%) parietal cells glucagon and histamine stimulated AC much more effectively than in the parietal cell depleted (15%, 7%) fractions. In contrast basal and histamine-stimulated [14C] aminopyrine uptake, an indirect measure of parietal cell H+ production, was not affected by glucagon. In homogenates of mucosal biopsy specimens 2 X 10(-7) mol/l glucagon enhanced AC activity by 76% (corpus) and 20% (antrum), respectively; 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. Histamine (10(-5), 10(-4), 10(-3) mol/l) and glucagon (10(-10) to 10(-6) mol/l) caused additive stimulation of AC. Ranitidine did not change AC in response to glucagon but abolished the effect of histamine. Our data demonstrate that glucagon stimulates an AC bound to the parietal cells. This response is not blocked by ranitidine suggesting that the glucagon action is mediated by a separate receptor, possibly by a glucagon-receptor. Furthermore we have shown that glucagon in contrast to its effects on AC does not affect H+ production.(ABSTRACT TRUNCATED AT 250 WORDS)
D000262:Adenylyl Cyclases / Q000032:analysis; D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000378:metabolism; D011899:Ranitidine / Q000494:pharmacology
D006632:Histamine; D011899:Ranitidine; D005934:Glucagon; D000262:Adenylyl Cyclases