Flavahan N A, Shimokawa H, Vanhoutte P M
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
J Pharmacol Exp Ther. 1991 Jan;256(1):50-5.
Activation of protein kinase C by phorbol esters inhibits the endothelium-dependent relaxations evoked by certain stimuli. The release of endothelium-derived relaxing factor can be evoked by a number of distinct subcellular processes, including activation of a pertussis toxin-sensitive G-protein. The aim of the present study was to determine whether or not the inhibitory effect of phorbol esters on endothelial function was associated with inhibition of the pertussis toxin-sensitive pathway. Rings of canine coronary artery were suspended for isometric tension recording in organ chambers filled with modified Krebs-Ringer bicarbonate solution, gassed with 95% O2-5% CO2 (37 degrees C). Treatment of arterial rings with pertussis toxin (100 ng/ml) or with phorbol myristate acetate (PMA, 10(-8) M) inhibited the endothelium-dependent relaxations produced by UK 14,304, an alpha-2 adrenergic agonist, leukotriene C4 or by NaF, a direct activator of G-proteins, but did not affect the endothelium-dependent relaxations produced by bradykinin or by A23187. If the arterial rings were first treated with pertussis toxin, PMA (10(-8) M) no longer inhibited the endothelium-dependent relaxations to NaF. Increasing the concentration of PMA (to 3 X 10(-8) and 10(-7) M) caused inhibition of responses to bradykinin. At higher concentrations, PMA (3 X 10(-7) and 10(-6)) also inhibited the relaxations evoked by A23187. The endothelium-independent relaxations evoked by nitroglycerin were not affected by PMA (10(-8) to 10(-6)).(ABSTRACT TRUNCATED AT 250 WORDS)
佛波酯激活蛋白激酶C可抑制某些刺激所诱发的内皮依赖性舒张。内皮源性舒张因子的释放可由多种不同的亚细胞过程所诱发，包括激活一种对百日咳毒素敏感的G蛋白。本研究的目的是确定佛波酯对内皮功能的抑制作用是否与抑制百日咳毒素敏感途径有关。将犬冠状动脉环悬挂于充满改良 Krebs-Ringer 碳酸氢盐溶液、通以 95% O₂ - 5% CO₂（37℃）的器官浴槽中进行等长张力记录。用百日咳毒素（100 ng/ml）或佛波醇肉豆蔻酸酯乙酸盐（PMA，10⁻⁸ M）处理动脉环，可抑制 UK 14,304（一种α₂肾上腺素能激动剂）、白三烯 C4 或 NaF（一种 G 蛋白直接激活剂）所产生的内皮依赖性舒张，但不影响缓激肽或 A23187 所产生的内皮依赖性舒张。如果动脉环先用百日咳毒素处理，PMA（10⁻⁸ M）就不再抑制对 NaF 的内皮依赖性舒张。增加 PMA 的浓度（至 3×10⁻⁸ 和 10⁻⁷ M）会抑制对缓激肽的反应。在更高浓度下，PMA（3×10⁻⁷ 和 10⁻⁶）也会抑制 A23187 所诱发的舒张。硝酸甘油所诱发的非内皮依赖性舒张不受 PMA（10⁻⁸ 至 10⁻⁶）的影响。（摘要截短于250字）
