Chronic surgical denervation of the rat vas deferens leads to an enhanced contractile response of the tissue to norepinephrine in vitro. Norepinephrine produces a higher rate of protein kinase C translocation to the particulate fraction of denervated tissues as compared with the paired, control vas deferens. Diacylglycerol generation in response to norepinephrine and contractile responses to phorbol diacetate were not altered by chronic denervation of the vas deferens. However, the contractile response to norepinephrine in these tissues was less susceptible to the inhibitory effects of the calcium channel blocker nifedipine. A potential role of protein kinase C in sensitizing the contractile apparatus to mobilized calcium in denervation supersensitivity is discussed.

1. The influence of catechol-O-methyltransferase inhibitor U-0521 on isotonic contraction of isolated rat vas deferens was examined to determine optimal concentration and nonspecific effects. 2. Maximum responses to (-)-epinephrine were increased at 0.4 microM and 1 microM concentrations of U-0521. Epinephrine responses were progressively decreased in the presence of higher concentrations (10 microM, 30 microM and 100 microM) of U-0521. 3. The response to the nonadrenergic agonist neurokinin A was similarly depressed in the presence of 100 microM U-0521. 4. U-0521 not only inhibits COMT, at concentrations above 1 microM it nonspecifically depresses contraction of the rat vas deferens by both adrenergic and nonadrenergic agonists.