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.
Kaschube
M
M
Institute of Pharmacology, Medical University of Lübeck, F.R.G.
Brasch
H
H
D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014649:Vas Deferens / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D001626:Bethanechol Compounds; D018723:Bethanechol; D002122:Calcium Chloride; D013755:Tetradecanoylphorbol Acetate; D009638:Norepinephrine