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.
Institute of Pharmacology, Medical University of Lübeck, F.R.G.
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Kaschube
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Brasch
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