Effects of Cholinergic, Histaminergic, and Peptidergic Stimulation on Pepsinogen Secretion by Isolated Human Peptic Cells

Abstract

Lanas AI, Anderson JW, Uemura N, Hirschowitz BI. Effects of cholinergic, histaminergic, and peptidergic stimulation on pepsinogen secretion by isolated human peptic cells. Scand J Gastroenterol 1994;29:678-683.

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 10⁶ cells, >90% pure and >95% viable. Secreted pepsinogen was measured with a sensitive hemoglobin digestion method at pH2. Results: Pepsinogen secretion was concentration-dependently stimulated by acetylcholine (ACh) (EC50 equals; 0.3 μM), cholecystokinin (CCK)-8 (2 nM), histamine (2 μM), and gastrin-1 (30 nM) but not by bombesin or pentagastrin. ACh stimulation was inhibited 40 times more potently by atropine (IC₅₀ equals; 12 nM) than by pirenzepine (IC₅₀ equals; 0.5 μM). Histamine was inhibited by 10⁻⁴ cimetidine. CCK-8 stimulation was inhibited 80% by the CCK-A-selective antagonist L364.718 (IC₅₀ equals; 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.

Key Words:

• Atropine
• cholecystokinin-A
• cholecystokinin-B receptors
• endoscopic biopsies
• muscarinic subtype
• pirenzepine