Endothelin stimulates tyrosine phosphorylation of p125 FAK and p130 Cas in rat cerebral cortex

Abstract

Stimulation of rat cerebral cortex with endothelin-1 (ET-1) caused an increase in the tyrosine phosphorylation of several proteins. Two of these phosphoproteins were identified by the immunoprecipitation assays as being the focal adhesion kinase p125 FAK and crk-associated substrate p130 Cas. This effect was time- and dose-dependent, with an EC 50 value of 3.9×10 −8 M. In addition, the cerebral cortex ET receptor subtype involved in this action was determined by using BQ-123 and BQ-788, which are ET A and ET B receptor antagonists respectively. Our results indicate that the ET-1 effect on protein tyrosine phosphorylation occurred through ET B receptors. The requirement for extracellular Ca 2+ on ET-1 action was also studied. ET-1-stimulated tyrosine phosphorylation of both p125 FAK and p130 Cas was abolished in the absence of external Ca 2+ or in the presence of nimodipine, a Ca 2+ channel-blocker. These results suggest that the ET-1-stimulated protein tyrosine phosphorylation was secondary to Ca 2+ influx through the dihydropyridine Ca 2+-channel. In slices where protein kinase C was inhibited, ET-1-stimulated tyrosine phosphorylation of both proteins was reduced. These results indicate that ET-1 modulates the tyrosine phosphorylation of specific proteins, which may be involved in adhesion processes in the brain.