Role of tyrosine kinases in norepinephrine-induced contraction of vascular smooth muscle

Worku Abebe, Devendra K. Agrawal

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Abstract

We used various probes to examine the involvement of tyrosine kinases in norepinephrine (NE)-induced contractile responses of the isolated rat aorta denuded of endothelium. The putative tyrosine kinase inhibitors, genistein and tyrphostin, significantly inhibited the contractile responses of the aorta to NE but not to potassium chloride (KC1). The protein tyrosine phosphatase inhibitor, sodium orthovanadate, also selectively potentiated the contractile response of the artery to NE. The inhibitory effect of genistein on NE-induced contraction was observed both in the absence and presence of extracellular calcium, which produced phasic and tonic contractile responses, respectively. The effect of genistein was more pronounced on the phasic contraction, suggesting that tyrosine kinases play a greater role in mediating the responses associated with the release of intracellular calcium. Genistein, however, had no effect on contraction elicited by the direct protein kinase C (PKC) activator phorbol 12,13 dibutyrate (PDB), providing evidence for the lack of involvement of tyrosine kinases in PKC-mediated contractile responses which contribute to the NE-induced tonic contraction. In contrast, genistein attenuated the contraction of the vessel evoked by the direct G-protein activator sodium fluoride (NaF), suggesting the involvement of tyrosine kinases in responses associated with G-protein activation. The data indicate that genistein- and tyrphostin-sensitive tyrosine kinases participate in NE-induced contraction of rat aortic smooth muscle. Although this may involve one or more steps in the signal transduction pathway, the enzymes appear to have a greater role in mediating the responses linked to the release of intracellular calcium and have no roles in certain other processes, including those mediated by PKC activation.

Original languageEnglish
Pages (from-to)153-159
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume26
Issue number1
StatePublished - 1995

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

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