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.