Epidermal growth factor inhibits amylase secretion and activation of phospholipase C in response to calcium-mobilizing secretagogues in rat pancreatic acini.
We recently showed that epidermal growth factor (EGF) inhibits cholecystokinin-octapeptide (CCK-8)-induced activation of phospholipase C and amylase release in isolated rat pancreatic acini. In the present study the effect of EGF on amylase release and inositol 1,4,5-trisphosphate (1,4,5-IP3) production in response to other calcium-mobilizing secretagogues, i.e. bombesin and carbachol, was examined in isolated pancreatic acini. EGF (17 nM) inhibited bombesin (100 nM)-stimulated amylase secretion from 10.3 +/- 1.7% to 0.8 +/- 1.6% of total above basal. Different from CCK-8, EGF reduced amylase release at both submaximal (< or = 1 microM) and supramaximal (> 1 microM) carbachol concentrations. Moreover, EGF (17 nM) inhibited bombesin-, carbachol-, and CCK-8-induced 1,4,5-IP3-production at five seconds after beginning of the incubation by 81 +/- 19%, 65 +/- 15%, and 60 +/- 12%, respectively. In conclusion, these results show that EGF inhibits amylase secretion in response to diverse calcium-mobilizing secretagogues in the exocrine pancreas and suggests that this inhibition is mediated by inhibition of phospholipase C.
Stryjek-Kaminska
D
D
Medizinische Klinik II, Universitätsklinikum, Frankfurt/Main.
Piiper
A
A
Caspary
W F
WF
Zeuzem
S
S
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000502:physiology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*
D004815:Epidermal Growth Factor; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D010738:Type C Phospholipases; D000681:Amylases; D012844:Sincalide; D001839:Bombesin; D002118:Calcium