EFFECTS OF CHOLINERGIC, HISTAMINERGIC, AND PEPTIDERGIC STIMULATION ON PEPSINOGEN SECRETION BY ISOLATED HUMAN PEPTIC CELLS

Background: Whereas pepsin secretion by the human stomach has been extensively investigated,the characteristics of the peptic cell cannot be fully understood from in vivo studies. We therefore studied isolated human peptic cells to test directly cellular responses to different agents. Methods: Eight endoscopic biopsy specimens yielded 10(6) cells, >90% pure and >95% viable. Secreted pepsinogen was measured with a sensitive hemoglobin digestion method at pH 2. Results: Pepsinogen secretion was concentration-dependently stimulated by acetylcholine (ACh) (EC(50) = 0.3 mu M), cholecystokinin (CCK)-8 (2 nM), histamine (2 mu M), and gastrin-I (30 nM) but not by bombesin or pentagastrin. ACh stimulation was inhibited 40 times more potently by atropine (IC50 = 12 nM) than by pirenzepine (IC50 = 0.5 mu M). Histamine was inhibited by 10(-4) cimetidine. CCK-8 stimulation was inhibited 80% by the CCK-A-selective antagonist L364,718 (IC50 = 12 nM) but not by the CCK-B-selective antagonist L365,260. Conclusion: Isolated human peptic cells from endoscopic biopsy specimens secrete pepsinogen in response to ACh > CCK-8 > histamine > gastrin-I. The human peptic cell muscarinic-cholinergic receptor is not of the M1 subtype, and the CCK-8 response is predominantly mediated by a CCK-A receptor subtype.