Takata Y, Ozawa J, Kato H
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Jpn J Pharmacol. 1991 Jul;56(3):337-48. doi: 10.1254/jjp.56.337.
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.
在预先用[3H]去甲肾上腺素（NE）加载的犬隐静脉中，研究了蛋白激酶C（PKC）激活剂和抑制剂对40 mM KCl诱发的氚溢出和收缩的影响。10(-11)-10(-7) M的12-O-十四烷酰佛波醇-13-乙酸酯（TPA）和佛波醇-12,13-二丁酸酯（PDBu）浓度依赖性地增强了KCl诱发的氚溢出，多粘菌素B（10(-5) M）和星形孢菌素（10(-7)或10(-6) M）可拮抗这种作用。PDBu（10(-8)和10(-7) M）而非TPA增强了KCl诱导的收缩。在PKC激活剂存在的情况下，只有星形孢菌素降低了KCl诱导的收缩。未能抑制外源性NE诱导收缩的多粘菌素B（3×10(-5) M）减弱了对KCl的两种反应。星形孢菌素（10(-6) M）不仅抑制了对KCl的两种反应，还抑制了外源性NE诱导的收缩。酚妥拉明（10(-6) M）几乎完全抑制了KCl诱导的收缩，并显著增强了诱发的氚溢出。在酚妥拉明处理的静脉中，PDBu（10(-8)和10(-7) M）仍增强了对KCl的两种反应。在酚妥拉明存在的情况下，额外用硝苯地平（10(-6) M）处理显著抑制了PDBu对KCl诱导收缩的增强作用，而不影响诱发的溢出。这些结果表明，PKC可能调节犬隐静脉肾上腺素能神经末梢KCl诱发的NE释放，并且PKC对突触前部位比突触后部位更敏感。
