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.