Tyrphostins inhibit secretagogue-induced 1,4,5-IP3 production and amylase release in pancreatic acini.
We examined the role of protein tyrosine kinase inhibitors (tyrphostins) in secretagogue-induced inositol 1,4,5-trisphosphate (1,4,5-IP3) production and amylase secretion in rat pancreatic acinar cells. The data show that various specific cell-permeant tyrphostins (methyl 2,5-dihydroxycinnamate, tyrphostin 25, and genistein) inhibited the cholecystokinin octapeptide-, carbachol-, and bombesin-induced 1,4,5-IP3 production and amylase release. In digitonin-permeabilized cells, tyrphostins decreased 1,4,5-IP3 accumulation and amylase release generated by directly stimulating G proteins with the weakly hydrolyzable GTP analogue guanosine 5'-O-(3-thiotriphosphate). Tyrphostins had no effect on vasoactive intestinal peptide-induced amylase secretion. In isolated pancreatic acinar membranes, cholecystokinin octapeptide caused a rapid increase in tyrosine phosphorylation of a synthetic peptide containing the 12-amino acid sequence around a tyrosine phosphorylation site in pp6osrc. These results provide evidence that tyrosine kinases are involved in the activation of phospholipase C by G protein-coupled receptors in pancreatic acinar cells.
Piiper
A
A
Department of Internal Medicine, University of Frankfurt/Main, Germany.
Stryjek-Kaminska
D
D
Stein
J
J
Caspary
W F
WF
Zeuzem
S
S
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D009570:Nitriles / Q000494:pharmacology*; D009994:Osmolar Concentration; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism*; D010539:Permeability; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D012844:Sincalide / Q000494:pharmacology; D020032:Tyrphostins
D002396:Catechols; D009570:Nitriles; D020032:Tyrphostins; C060152:tyrphostin 47; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D004815:Epidermal Growth Factor; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D011505:Protein-Tyrosine Kinases; D000681:Amylases; D012844:Sincalide; D001839:Bombesin