A tyrosine kinase regulates α-adrenoceptor-stimulated contraction and phospholipase D activation in the rat aorta

Since previous studies had indicated a role for tyrosine kinases in α2- adrenoceptor-induced contractile responses in other blood vessels, as well as in the activation of phospholipase D, we examined the sensitivity of these responses in rat aorta to the tyrosine kinase inhibitor genistein. Contractions induced by both noradrenaline and the α2-adrenoceptor- selective agonist UK14304 (5-bromo-6-[2-imidazolin-2-yl-amino]-quinoxaline) were fully inhibited by genistein, with the latter responses being more sensitive. Contractions induced by high K+ buffer were also inhibited, but to a lesser extent. Both agonists caused a stimulation of phospholipase D activity, which could be blocked by pretreatment with pertussis toxin, indicating involvement of either G(i) or G(o). Genistein completely inhibited the agonist-induced phospholipase D activity and also substantially reduced the basal level of phospholipase D activity. Pretreatment with either the α1-adrenoceptor antagonist prazosin or the α2-adrenoceptor antagonist rauwolscine was also effective in eliminating the agonist-induced increase of phospholipase D. These results indicate that a tyrosine kinase-regulated phospholipase D plays a critical role in α-adrenoceptor-induced contractions of the rat aorta and that stimulation of both α1- and α2-adrenoceptors is essential to allow phospholipase activation.