Abstract

We have tested the role of various protein kinases in noradrenaline-induced, alpha1A-adrenoceptor-mediated constriction of mesenteric and intrarenal rat microvessels. The protein kinase C inhibitors, H7 and staurosporine, inhibited constriction in both vessel types in concentrations which also inhibit myosin light chain kinase. The more selective protein kinase C inhibitors, bisindolylmaleimide I and Gö 6976, did not inhibit microvessel constriction in concentrations selective for protein kinase C. Moreover, the protein kinase C-activating phorbol ester, phorbol-12-myristate-13-acetate, did not cause constriction. The tyrosine kinase inhibitors, genistein and tyrphostin 23, inhibited constriction in concentrations compatible with tyrosine kinase inhibition. An inhibitor of the extracellular signal-regulated kinase cascade, PD 98059, also caused concentration-dependent inhibition. While chelation of extracellular Ca2+ abolished noradrenaline-induced constrictions, the Ca2+-ATPase inhibitor, thapsigargin, had no effects. We conclude that tyrosine kinases and extracellular signal-regulated kinase (but not protein kinase C) may be involved in noradrenaline-induced rat mesenteric and intrarenal microvessel constriction but this appears to occur independently of an effect on sarcoplasmic Ca2+ storage.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.