title: Prostaglandin E2 inhibits secretagogue-induced enzyme secretion from rat pancreatic acini.
abstract: Prostaglandins of the E type may have a potential role in pancreatic physiology and pathophysiology. Because prostaglandins of the E type inhibit HCl secretion in parietal cells via a specific receptor by inhibition of adenylylcyclase, we studied whether a similar mechanism exists in the exocrine pancreas. Isolated rat pancreatic acini were incubated with various concentrations of secretagogues, such as cholecystokinin-octapeptide (CCK-8), bombesin, carbachol, and vasoactive intestinal peptide (VIP), in the absence or presence of prostaglandin E2 (PGE2), and amylase secretion was measured. For receptor binding studies, acini and pancreatic membranes were incubated with [3H]PGE2 and either unlabeled PGE2 or other types of prostaglandins. PGE2 (10(-13) to 10(-5) M) did not inhibit basal amylase secretion. However, CCK-8-stimulated secretion was significantly inhibited. Stimulation of secretion by bombesin, carbachol, VIP, and secretin was also inhibited by PGE2, but not as pronounced as CCK-8-stimulated secretion. The formation of inositol 1,4,5-trisphosphate induced by CCK-8 was markedly inhibited by simultaneous incubation with PGE2. Furthermore, PGE2 slightly but significantly reduced the CCK-8-induced efflux of 45Ca2+ from prelabeled acini. Intact acini and a membrane fraction bound [3H]PGE2 and this function could be equally competed by either unlabeled PGE2 or PGE1 in contrast to less-related prostaglandins such as PGF2 alpha, PGD2, and prostacyclin. We conclude that prostaglandins of the E type inhibit pancreatic enzyme secretion stimulated by various secretagogues. This function is mediated via specific receptors for PGE. With regard to CCK-8-stimulated secretion this function may be mediated by an inhibition of formation of inositol 1,4,5-trisphosphate.
authors.affiliation: Medizinische Poliklinik, University of Würzburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Mössner
authors.forename: R
authors.initials: R
authors.lastname: Secknus
authors.forename: G M
authors.initials: GM
authors.lastname: Spiekermann
authors.forename: C
authors.initials: C
authors.lastname: Sommer
authors.forename: M
authors.initials: M
authors.lastname: Biernat
authors.forename: H
authors.initials: H
authors.lastname: Bahnsen
authors.forename: W
authors.initials: W
authors.lastname: Fischbach
mesh_terms: D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007700:Kinetics; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D011453:Prostaglandins / Q000494:pharmacology; D014176:Protein Biosynthesis; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000502:physiology; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000502:physiology; D018078:Receptors, Prostaglandin E; D012844:Sincalide / Q000494:pharmacology
chemical_list: D011453:Prostaglandins; D011949:Receptors, Cholecystokinin; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D000001:Calcimycin; D003994:Bucladesine; D015544:Inositol 1,4,5-Trisphosphate; D000681:Amylases; D015232:Dinoprostone; D012844:Sincalide