Epidermal growth factor inhibits hormone- and fibroblast growth factor-induced activation of phospholipase C in rat pancreatic acini.
Epidermal growth factor (EGF) inhibits cholecystokinin-octapeptide-stimulated amylase release and inositol 1,4,5-trisphosphate (1,4,5-IP3) production in isolated rat pancreatic acini. In the present study, pancreatic acini were used to investigate the effect of EGF on amylase release and 1,4,5-IP3 production induced by secretagogues that activate either phospholipase C-beta (carbachol, bombesin) or phospholipase C-gamma [basic fibroblast growth factor (bFGF)]. The results show that EGF (100 ng/ml) inhibited bombesin (0.1 nM-1 microM)-induced amylase release almost completely. Similarly, the effect of EGF on carbachol-stimulated amylase release was substantial at submaximal (0.1 microM: 44% inhibition), maximal (1 microM: 75% inhibition), and supramaximal (100 microM: 33% inhibition) carbachol concentrations. EGF reduced amylase release at submaximal bFGF concentrations (0.1 nM: 40% inhibition), but not at supramaximal bFGF concentrations (1 and 10 nM). EGF decreased the peak increase of 1,4,5-IP3 in response to bombesin and carbachol (5 s after beginning of the incubation) and bFGF (15 s after beginning of the incubation) by 81 +/- 19%, 65 +/- 15%, and 56 +/- 18%, respectively. Receptor binding characteristics for secretagogues that activate phospholipase C were not influenced by coincubation with EGF excluding heterologous transmembrane receptor modulation. These results suggest that EGF inhibits the action of phospholipase C-beta- and gamma-isoenzyme-activating secretagogues in the exocrine pancreas by a postreceptor mechanism.
Stryjek-Kaminska
D
D
II. Medical Department, University of Frankfurt a. M., Germany.
Piiper
A
A
Caspary
W F
WF
Zeuzem
S
S
D000681:Amylases / Q000187:drug effects / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D001667:Binding, Competitive; D001839:Bombesin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*
D007527:Isoenzymes; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D010738:Type C Phospholipases; D000681:Amylases; D012844:Sincalide; D001839:Bombesin