Pepsin secretion: neurohumoral regulation and drug effects.
The regulation of pepsin secretion was studied in the in vitro perfused mouse stomach. In contrast to acid secretion, basal pepsin release was not inhibited by 10(-4) M carbonyl cyanide m-chlorophenylhydrazine (CCCP) and by N2-induced hypoxia. Both secretions were not affected by 10(-3) M cimetidine, 10(-3) M atropine or cycloheximide (2 mg i.p. + 10(-5) M). Secretory responses to classical stimulants were similar to those obtained under in vivo conditions: carbamylcholine (CCH) and histamine stimulated acid and pepsin secretion in parallel, with a maximal pepsin/acid ration of 34 +/- 4 (mean +/- SEM) and 40 +/- 5, respectively. CCH-induced pepsin secretion was inhibited by atropine and pirenzepine. Dibutyrylic cyclic AMP(db-cAMP) strongly stimulated pepsin release. This stimulation was partially inhibited by trifluoperazine. Pentagastrin was a weak stimulant of pepsin secretion (pepsin/acid ratio: 10 +/- 3), whereas 10(-4) M bombesin and 10(-6) M salmon calcitonin had no effect. Omeprazole (H168/68) strongly inhibited basal acid secretion and stimulated pepsin release in a dose-and energy-dependent fashion. In contrast to acid, basal pepsin release probably represents an 'overflow secretion'. Although pepsin and acid are usually stimulated in parallel, dissociated responses are obtained under in vitro conditions, indicating that separate regulatory pathways exist.
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism; D005755:Gastrins / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008954:Models, Biological; D009853:Omeprazole; D010276:Parasympatholytics / Q000494:pharmacology*; D010434:Pepsin A / Q000378:metabolism*; D012636:Secretory Rate / Q000187:drug effects
D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D005755:Gastrins; D010276:Parasympatholytics; D003994:Bucladesine; D001285:Atropine; D002927:Cimetidine; D006632:Histamine; D002217:Carbachol; D003513:Cycloheximide; D010434:Pepsin A; D009853:Omeprazole