Pre- and postjunctional effects of phorbol 12-myristate-13-acetate in the mouse vas deferens

The protein kinase C stimulator phorbol 12-myristate-13-acetate (PMA) increased the release of noradrenaline from field-stimulated mouse vasa deferentia and antagonized the inhibitory effect of xylazine and FK 33-824. The mechanical response to field stimulation was not modified by PMA in unpretreated vasa, but the contractility was partly restored when the stimulation-response curve had been depressed by xylazine or FK 33-824. In contrast, PMA decreased the contractile response to exogenous noradrenaline and bethanechol. A similar but smaller reduction was obtained with 1,2-dioctanoyl-sn-glycerol. In vasa depolarized by KCl, PMA and verapamil reduced the amplitude of contractions elicited by CaCl2. Only the effect of verapamil could be reversed by the calcium ionophore A 23187, while the effect of PMA was greatly attenuated in muscles pretreated with ouabain. Phorbol 12-myristate-13-acetate-4-O-methylether was ineffective in all experiments. These results suggest that PMA increases noradrenaline release (prejunctional effect) and decreases vasal contractility (postjunctional effect) by activation of protein kinase C.