Effects of prostaglandins on gastrin release from canine antral mucosal cells in primary culture

Abstract

Evidence in vivo indicates that endogenous and exogenous prostaglandins can alter gastrin secretion. We have used primary cultures containing canine antral G-cells to study the cellular actions of prostaglandins on gastrin secretion, comparing the effects of prostaglandin E2 (PGE2) and its synthetic analogue enprostil. Enprostil (10(-10)-10(-6) M) inhibited gastrin secretion in response to bombesin, carbachol, and forskolin, the latter a receptor-independent activator of adenylate cyclase. This inhibition by enprostil was reversed by treatment with pertussis toxin (200 ng/ml, 8 h). However, enprostil did not inhibit the postreceptor stimuli 8-bromoadenosine 3',5'-cyclic monophosphate (10(-3) M), calcium ionophore A-23187 (10(-7) M), or 4 beta-phorbol 12-myristate 13-acetate (10(-8) M). In contrast, whereas PGE2 inhibited forskolin-stimulated gastrin release, PGE2 did not inhibit the response to carbachol or bombesin in control cultures. However, in pertussis toxin-treated cultures, PGE2 inhibition was reversed and, in contrast, the responses to bombesin, carbachol, and possibly forskolin were augmented. Indomethacin at a dose of 10(-5) M did not alter basal or bombesin-stimulated gastrin secretion. However, the somatostatin antibody CURE-S6 enhanced the response to forskolin and enhanced inhibition by PGE2, suggesting that endogenous somatostatin produced an inhibitory tone in these cultures and excluding the possibility that PGE2 acted via release of endogenous somatostatin. Our data suggest that in cultured antral cells gastrin release is regulated by inhibitory and stimulatory prostaglandin mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

The mechanism of inhibitory action of secretin on gastric acid secretion in conscious rats.

“…However, their observation was in contrast to the report that prostaglandin synthesis inhibition by indomethacin did not influence somatostatin-induced inhibition of either bethanechol-stimulated acid secretion in both conscious and anaesthetized rats (Mogard, Kauffman, Pehlevanian, Golanska, Elashoff & Walsh, 1985), or pentagastrin-stimulated gastric acid and pepsin secretion in conscious cats (Albinus, Gomez-Pan, Hirst & Shaw, 1985). Also, immunoneutralization of somatostatin did not suppress the inhibitory effect of prostaglandin E2 on forskolin-stimulated gastrin release in canine antral mucosal cell culture (Schepp et al 1994), indicating that inhibition by prostaglandin E2 was not mediated by somatostatin. From the present study in conscious rats, it is apparent that both antisomatostatin serum and indomethacin reverse the inhibition by secretin of pentagastrinstimulated acid secretion and both augment basal acid secretion, whereas antisomatostatin serum also augments the pentagastrin-stimulated acid secretion.…”

Bombesin-induced gastrin release from canine G cells is stimulated by Ca2+ but not by protein kinase C, and is enhanced by disruption of rho/cytoskeletal pathways.

“…G cells are stimulated by gastrin-releasing peptide (GRP)/bombesin (1)(2)(3). Sympathomimetics, acetylcholine, prostaglandin, adenosine, and somatostatin are other substances known to act through specific receptors on canine G cells (1,(4)(5)(6)(7). All these receptors belong to the superfamily of seven-transmembrane, G-protein-coupled receptors.…”

Changes of Gastric Juice Microenvironment in Patients with Fundic Gland Polyp and Hyperplastic Polyp

“…In our study, increased gastric juice gastrin-17 level was observed among patients with HPs and fundic gland polyps. Gastrin has been reported to interact with prostaglandins signaling pathway [30,31] that plays pivotal roles in the mucosal integrity and the normal function of gastrointestinal tract such as the secretion of gastric juice [32][33][34]. The duodenal ulcer is related with reduced PGE2 level [32,34,35]; however, the role of PGE2 in regulating gastric polyps development is unclear.…”