Abstract
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 × 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.
