Effects of wortmanninon alpha-1/alpha-2 adrenergic receptor-mediated contractile responses in rabbit vascular tissues

The inhibitory effect of wortmannin (WO), a fungus-derived protein kinase inhibitor, was assessed on contractile responses elicited by phenylephrine-induced α1 (α1R) and UK 14304- induced α2-adrenergic receptor (α2R) stimulation in the rabbit aorta and saphenous vein, respectively. In agonist dose- response studies, WO caused a noncompetitive inhibition of both α1R and α2R responses, but was more potent againstα2R. Maximally effective single-dose responses at both receptors were less sensitive to WO. The initialα1R contractile response, associated with intracellular Ca2+ release and myosin light chain kinase activation, was relatively insensitive to WO, while the Ca2+ influx-dependent tonic contraction was more sensitive. Contractions induced by high K+ buffer were relatively insensitive to WO in both the aorta and saphenous vein. These results indicate that WO inhibits receptor-initiated Ca2+ influx-dependent contractile responses such as those caused by α2R stimulation and the sustained phase of α1R stimulation more readily than Ca2+ release-dependent responses.