Tyrosine kinase inhibitors attenuate "capacitative" Ca2+ influx in rat pancreatic acinar cells.
The effect of several tyrosine kinase inhibitors was tested on Ca2+ influx mediated by thapsigargin-and CCh-induced intracellular store depletion. Genestein inhibited Ca2+ influx in a concentration dependent manner without affecting Ca2+ release or Ca2+ pumping activity. A measureable effect was observed at 3 microM with total inhibition of influx seen at 100 microM. Tyrphostin A25 (300 microM; 78% inhibition) and methyl 2,5 dihydroxycinnamate (10 microM; 51% inhibition) also inhibited Ca2+ influx. The degree of attenuation was not markedly altered by preincubation of the inhibitors. Genestein also inhibited Ca2+ influx induced by CCh. These data indicate that inhibition of Ca2+ influx could in part underlie the previously reported inhibition of enzyme secretion by these agents.
Yule
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DI
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109.
Kim
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Williams
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JA
D000818:Animals; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology*; D002934:Cinnamates / Q000494:pharmacology*; D019833:Genistein; D017136:Ion Transport / Q000187:drug effects; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D020032:Tyrphostins
D002396:Catechols; D002934:Cinnamates; D007529:Isoflavones; D009570:Nitriles; D013729:Terpenes; D020032:Tyrphostins; C060152:tyrphostin 47; D001464:Barium; C067472:methyl 2,5-dihydroxycinnamate; D019284:Thapsigargin; D002217:Carbachol; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D002118:Calcium