title: Interaction among secretagogues on pepsinogen secretion from rat gastric chief cells.
abstract: We examined the interaction among secretagogues that stimulate pepsinogen secretion through different pathways in vivo and in vitro. In in vitro study, a combined administration of secretin and carbachol or cholecystokinin octapeptide (CCK-8) to the culture medium of chief cells potentiated pepsinogen secretion. Moreover, the response induced by carbachol or CCK-8 with forskolin was greater than that with secretin. We examined the interaction among receptor-related second mediators, and found that carbachol- or CCK-8-induced intracellular Ca2+ concentration ([Ca2+]i) increase was not affected by secretin or forskolin. Both these substances, however, significantly reduced secretin-induced cAMP production. On the contrary, CCK-8 significantly increased forskolin-induced cAMP production, while carbachol increased it slightly. Calcium ionophore, A23187, or protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), did not alter secretin- or forskolin-induced cellular cAMP production; and the reductive effect of carbachol or CCK-8 on secretin-induced cAMP production was restored by their competitive antagonists, atropine or lorglumide. EC50 of those antagonists was almost the same value as IC50 on pepsinogen secretion and [Ca2+]i increase. These results indicate that secretin-induced cAMP production is interfered with by receptor related agonists like CCK-8 and carbachol. It may be suggested that there is a kind of "cross-talk," between the adenylate cyclase system, that is, the secretin receptor, and carbachol or CCK-8 receptor. The interactions between secretin and other secretagogues (carbachol, CCK-8, tetragastrin and histamine) were examined using the perfused rat stomach.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: S
authors.initials: S
authors.lastname: Tani
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D004347:Drug Interactions; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D010435:Pepsinogens / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical
chemical_list: D010435:Pepsinogens; D000242:Cyclic AMP; D002118:Calcium