Selectivity of quercetin inhibition on stimulated amylase release in rat pancreatic acini.
Quercetin (Q) has been shown to inhibit Ca2+-dependent processes. The present study evaluates the effect of Q on amylase release stimulated by various agonists in dispersed rat pancreatic acini. Q inhibited amylase release stimulated by an optimal concentration of carbachol. The inhibition was dependent on Q concentration. Preincubation with Q was not necessary. Maximal inhibition (up to 60% of control) was reached at 50 microM of Q and was completely reversible. Full responsiveness of the acini to agonist stimulation was reestablished as early as 5 min upon the removal of Q. At 50 microM, Q inhibited stimulated amylase release by optimal concentrations of tetradecanoylphorbol-13-acetate (TPA) (10(-6) M), A23187 (3 x 10(-6) M), cholecystokinin C-terminal octapeptide (CCK-OP) (10(-9) M) and carbachol (3 x 10(-6) M), but not by vasoactive intestinal polypeptide (VIP) (3 x 10(-7) M). Instead, Q promoted amylase release stimulated by VIP. The inhibition of amylase secretion by Q occurred only at near optimal, optimal, and supraoptimal concentrations of TPA, A23187, CCK-OP, and carbachol. The potentiation effect of Q on VIP-stimulated amylase secretion was, however, seen at all concentrations of VIP used (10(-8) to 10(-6) M). Quercetin also inhibited protein kinase C activity from rat pancreas in a dose-dependent manner. Maximal inhibition (approximately 85%) was seen at 100 microM of Q. These results provide further support that the intermediary steps for stimulated enzyme secretion in pancreatic acini by TPA, A23187, CCK-OP, and carbachol involve calmodulin and/or protein kinase C, whereas VIP does not.(ABSTRACT TRUNCATED AT 250 WORDS)
Lee
P C
PC
Division of Gastroenterology and Nutrition, Children's Hospital of Buffalo, NY 14222.
Shimizu
K
K
Rossi
T M
TM
Cumella
J C
JC
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000494:pharmacology
D005419:Flavonoids; D002217:Carbachol; D011794:Quercetin; D011493:Protein Kinase C; D000681:Amylases; D012844:Sincalide