Phorbol ester-induced contraction of arterial smooth muscle and inhibition of alpha-adrenergic response.
The influence of the phorbol ester, 12-o-tetradecanoylphorbol-13 acetate (TPA) on the contractility of rat and rabbit aorta was assessed. At 10(-8) to 10(-5)M TPA produced a gradual contraction of rat aorta, while rabbit aorta gave only a small contraction at 10(-5)M. Contractions were irreversible and dependent on extracellular Ca2+. Associated with TPA-induced contraction, alpha-adrenergic receptor responses of the rat were inhibited in a noncompetitive manner, while rabbit responses were little affected. Since TPA activates phospholipid-dependent protein kinase C in a manner analogous to endogenous diacylglycerol, a critical role for the latter in alpha-adrenergic events is suggested.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D010704:Phorbols / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D010704:Phorbols; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D004533:Egtazic Acid; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium