Source(s) of activator calcium for noradrenaline-induced vasoconstriction in the perfused rabbit isolated ovarian vascular bed - A role for tyrosine kinase

The effects of Ca2+ withdrawal and agents affecting Ca2+ translocation on a lpha(1)-adrenoceptor-mediated vasoconstrictor responses in the perfused rab bit ovarian vascular bed were studied. Noradrenaline-induced vasoconstricti on was lost in a Ca2+-free Krebs' solution, and the rate of loss of the res ponse was accelerated by EGTA (2 mM). Noradrenaline-induced vasoconstrictio n and SDZ NVI085-induced vasoconstriction were concentration-dependently in hibited by verapamil and nifedipine. These agents were, however, more effec tive against KCl-induced responses. Cyclopiazonic acid, an intracellular Ca 2+ depletor, concentration-dependently inhibited noradrenaline-induced resp onses and abolished the response in Ca2+-free Krebs' solution. GF 109203X a nd polymyxin B, inhibitors of protein kinase C (PKC), had no significant ef fect on noradrenaline-induced responses. Tyrosine kinase inhibitors, genist ein and erbstatin, inhibited noradrenaline-induced vasoconstriction in the perfused rabbit ovarian vascular bed. The results would suggest that both e xtracellular Ca2+ and intracellular Ca2+ participate in noradrenaline-induc ed vasoconstrictor responses in the perfused rabbit ovarian vascular bed. T he results would also suggest that tyrosine kinase and not protein kinase C activation has a role in such effects. (C) 1999 Elsevier Science Inc. All rights reserved.