Presynaptic sites of isolated canine saphenous veins are more sensitive to protein kinase C than postsynaptic ones.
Effects of protein kinase C (PKC) activators and inhibitors on both tritium overflow and contraction evoked by 40 mM KCl were studied in canine saphenous veins preloaded with [3H]norepinephrine (NE). 12-O-Tetradecanoylphorbol 13-acetate (TPA) and phorbol 12,13-dibutyrate (PDBu) at 10(-11)-10(-7) M enhanced concentration-dependently the KCl-evoked tritium overflow, which was antagonized by polymyxin B (10(-5) M) and staurosporine (10(-7) or 10(-6) M). PDBu (10(-8) and 10(-7) M), but not TPA, potentiated the KCl-induced contraction. Only staurosporine reduced the KCl-induced contraction in the presence of PKC activators. Polymyxin B (3 X 10(-5) M) which failed to inhibit exogenous NE-induced contraction attenuated both responses to KCl. Staurosporine (10(-6) M) suppressed not only both the responses to KCl but also exogenous NE-induced contraction. Phentolamine (10(-6) M) inhibited almost completely the KCl-induced contraction and augmented remarkably the evoked tritium overflow. PDBu (10(-8) and 10(-7) M) still potentiated both responses to KCl in the phentolamine-treated veins. An additional treatment with nifedipine (10(-6) M) inhibited markedly the potentiation of the KCl-induced contraction by PDBu in the presence of phentolamine without affecting the evoked overflow. These results suggest that PKC may modulate KCl-evoked NE release from the adrenergic nerve endings of canine saphenous veins and that PKC is more sensitive to presynaptic than postsynaptic sites.
Takata
Y
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Ozawa
J
J
Kato
H
H
D000818:Animals; D004285:Dogs; D004789:Enzyme Activation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011112:Polymyxin B / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D012501:Saphenous Vein / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014316:Tritium; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D014316:Tritium; D015240:Phorbol 12,13-Dibutyrate; D011189:Potassium Chloride; D011493:Protein Kinase C; D011112:Polymyxin B; D013755:Tetradecanoylphorbol Acetate; D009638:Norepinephrine