Effects of prostaglandins on gastrin release from canine antral mucosal cells in primary culture.
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)
Schepp
W
W
Center for Ulcer Research and Education, University of California Gastroenteric Biology Center, Los Angeles.
Chan
C B
CB
Giraud
A S
AS
Avedian
D
D
Chen
M C
MC
Chew
P
P
Walsh
J H
JH
Soll
A H
AH
D037361:Adenylate Cyclase Toxin; D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000502:physiology; D004285:Dogs; D016620:Enprostil / Q000494:pharmacology; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005755:Gastrins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D037342:Pertussis Toxin; D011453:Prostaglandins / Q000494:pharmacology*; D011706:Pyloric Antrum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D005755:Gastrins; D011453:Prostaglandins; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D016620:Enprostil; D015232:Dinoprostone