Potentiation of cholecystokinin-induced amylase release by peptide VIP in guinea pig pancreatic acini.
The mechanism of the potentiating effect of vasoactive intestinal peptide (VIP) on cholecystokinin (CCK-8)-induced amylase release was studied in isolated and perifused pancreatic acini of the guinea pig. VIP (30 pM-10 nM) potentiated CCK-8 (100 pM)-induced amylase release. Unexpectedly, VIP inhibited CCK-8-induced intracellular Ca2+ oscillations. Forskolin (10 microM), an activator of adenylate cyclase, potentiated CCK-8 (100 pM)-induced amylase release with a time course similar to that observed with VIP. Caffeine (20 mM) inhibited both amylase release and Ca2+ oscillations in response to CCK-8, suggesting that inhibition of Ca2+ oscillations does not necessarily lead to a potentiation of amylase release. When intracellular Ca2+ concentration ([Ca2+]c) was raised by thapsigargin (10 microM), a selective inhibitor of Ca(2+)-ATPase in the endoplasmic reticulum (ER), VIP (10 nM) induced significantly greater amylase release than that induced by VIP alone. When [Ca2+]c was lowered by preincubation with BAPTA-AM (25 microM), a cell-permeant Ca2+ chelator, VIP-induced amylase release was completely abolished. These results suggest that VIP, in spite of its inhibitory action on Ca2+ oscillations, facilitates a Ca(2+)-dependent process distal to the increase in [Ca2+]c to potentiate CCK-8-induced amylase release.
Tanaka
K
K
Department of Physiology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Shibuya
I
I
Kanno
T
T
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002766:Cholecystokinin / Q000494:pharmacology*; D005576:Colforsin / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology*; D010477:Perfusion; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D002110:Caffeine; D002766:Cholecystokinin; D000681:Amylases; D002118:Calcium