TYROSINE KINASES PARTICIPATE IN ALPHA(1A)-ADRENOCEPTOR-MEDIATED VASOCONSTRICTION IN PERFUSED RAT HINDLIMB

AIM: To determine whether or not tyrosine kinase is involved in the si gnal transduction of ala-adrenoceptors. METHODS: Effects of various ph armacological probes on norepinephrine NE)-induced vasopressor respons es were determined in the perfused rat hindlimb. RESULTS: The putative tyrosine kinase inhibitors, genistein, and tyrphostin, significantly inhibited the vasopressor responses induced by NE but not that induced by KCl. The protein-tyrosine-phosphatase inhibitor, sodium orthovanad ate, selectively potentiated the vasopressor responses induced by NE. Neither genistein nor tyrphostin had effect on the contraction elicite d by phorbol 12-myristate 13-acetate. In contrast, both genistein and tyrphostin attenuated the vasopressor responses evoked by NaF. CONCLUS ION: The genistein- and tyrphostin-sensitive tyrosine kinases particip ate in alpha(1A)-adrenoceptor-mediated vasoconstriction in perfused ra t hindlimb.