Prostaglandin E analogue inhibition of pancreatic enzyme secretion.
The effect of native prostaglandins and their methylated analogues on pancreatic enzyme secretion remains unclear, with previous studies reporting inconsistent results. To determine whether the E series prostaglandins directly influence pancreatic secretion, we studied the effect of rioprostil, a prostaglandin E1 analogue, and 16,16-dimethyl prostaglandin E2 (DMPGE2), a prostaglandin E2 analogue, on enzyme release from dispersed guinea pig pancreatic acini. Basal amylase release (4.3 +/- 0.6% of total acinar content) was not altered by either analogue (10(-10)-10(-5) M). A 50% inhibition of maximal cholecystokinin stimulation (10(-9) M; 28.8 +/- 1.2%) was seen with rioprostil (10(-7) M; 14.6 +/- 1.3%) and DMPGE2 (10(-6) M; 15.9 +/- 0.7%) (both p less than 0.005). Prostaglandin inhibition of carbachol-stimulated amylase was less pronounced. The most effective inhibitory dosage with maximal carbachol (10(-5) M; 30.2 +/- 1.9%) was 10(-6) M for both rioprostil (19.2 +/- 1.6%) and DMPGE2 (22.4 +/- 1.7%) (both p less than 0.005). Incubation of acini with A23187, phorbol ester, and 1-oleoyl-2-acetyl-glycerol resulted in a dose-dependent increase in amylase release that was not altered by maximal concentrations of either prostaglandin analogue. Our results indicate that rioprostil and DMPGE2 can directly inhibit pancreatic acinar secretion. This effect appears to occur before activation of the inositol phospholipid system.
Zucker
K A
KA
Department of Surgery, Yale University School of Medicine, West Haven, Connecticut.
Bilchik
A J
AJ
Modlin
I M
IM
Adrian
T E
TE
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology*; D011458:Prostaglandins E / Q000494:pharmacology; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D016630:Rioprostil; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D004075:Diglycerides; D011458:Prostaglandins E; D011459:Prostaglandins E, Synthetic; D000001:Calcimycin; D016630:Rioprostil; C038237:1-oleoyl-2-acetylglycerol; D002217:Carbachol; D002766:Cholecystokinin; D000681:Amylases; D015064:16,16-Dimethylprostaglandin E2; D013755:Tetradecanoylphorbol Acetate