Rubanyi G M, Desiderio D, Luisi A, Johns A, Sybertz E J
Department of Pharmacology, Berlex Laboratories, Cedar Knolls, New Jersey.
J Pharmacol Exp Ther. 1989 Jun;249(3):858-63.
The effects of phorbol esters on endothelium-dependent relaxations evoked by ACh and the calcium ionophore A23187 were analyzed in isolated canine femoral and coronary arteries mounted in organ chambers or in a bioassay system. In rings of femoral and coronary arteries, phorbol 12,13-dibutyrate (PDBu) (10(-7) M) evoked contraction (ED50 2.9 x 10(-8) M) and depressed endothelium-dependent relaxations to ACh (4-fold increase in ED50 and 72% depression of maximal response). PDBu depressed maximal relaxations to A23187 by 50% but had no effect on ED50. The inactive phorbol ester 4-alpha-phorbol didecanoate (10(-7) M) did not evoke contractions and had no effect on endothelium-dependent relaxations to ACh or A23187. Endothelium-independent relaxations to sodium nitroprusside were not effected by PDBu (10(-7) M) in femoral or coronary arteries. In bioassay experiments, selective treatment of perfused femoral artery segments with PDBu (10(-8)-10(-6) M) caused concentration-dependent inhibition of basal and ACh- (10(-6) M) and A23187-(10(-6) M) induced release of endothelium-derived relaxing factor (EDRF) (as assessed by relaxation of superfused bioassay coronary artery rings without endothelium). PDBu inhibited these responses with different potency: basal (10(-8) M) greater than ACh (10(-7) M) much greater than A23187 (only partial inhibition at 10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)
在安装于器官浴槽或生物测定系统中的离体犬股动脉和冠状动脉上，分析了佛波酯对乙酰胆碱（ACh）和钙离子载体A23187所诱发的内皮依赖性舒张的影响。在股动脉和冠状动脉环中，佛波醇12,13 - 二丁酸酯（PDBu）（10⁻⁷M）诱发收缩（半数有效量[ED50]为2.9×10⁻⁸M），并抑制对ACh的内皮依赖性舒张（ED50增加4倍，最大反应降低72%）。PDBu使对A23187的最大舒张降低50%，但对ED50无影响。无活性的佛波酯4-α-佛波醇二癸酸酯（10⁻⁷M）不诱发收缩，对ACh或A23187所诱发的内皮依赖性舒张也无影响。在股动脉或冠状动脉中，PDBu（10⁻⁷M）对硝普钠所诱发的非内皮依赖性舒张无影响。在生物测定实验中，用PDBu（10⁻⁸ - 10⁻⁶M）选择性处理灌注的股动脉段，导致对基础状态以及ACh（10⁻⁶M）和A23187（10⁻⁶M）所诱导的内皮衍生舒张因子（EDRF）释放产生浓度依赖性抑制（通过无内皮的灌注生物测定冠状动脉环的舒张来评估）。PDBu以不同效力抑制这些反应：基础状态（10⁻⁸M）＞ACh（10⁻⁷M）＞＞A23187（在10⁻⁶M时仅部分抑制）。（摘要截短于250字）
