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.