Chiu A T, Wong P C, Timmermans P B
Medical Products Department, E.I. du Pont de Nemours & Company (Inc.), Wilmington, Delaware.
J Pharmacol Exp Ther. 1987 Nov;243(2):577-83.
The influx of 45Ca++ produced by l-norepinephrine (3 X 10(-7) or 10(-5) M) and K+ (100 mM) in rat aorta was not significantly influenced by phenoxybenzamine (1 or 3 X 10(-8) M) present for 5 or 10 min. However, the l-norepinephrine (3 X 10(-7) or 10(-5) M)-mediated 45Ca++ efflux was markedly attenuated by this treatment. Higher concentrations of phenoxybenzamine, as well as extension of the time of exposure, impaired the 45Ca++ influx to l-norepinephrine, but not that to K+. In contrast, prazosin (10(-9)-10(-7) M), as well as N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (10(-7) or 10(-6) M for 5 or 10 min), was equally effective in antagonizing the 45Ca++ in and efflux caused by l-norepinephrine. Exposure of rat aorta to 1.3 X 10(-9) M phenoxybenzamine for 30 min significantly shifted the log concentration-contractile response curve to the full alpha-1 adrenoceptor agonist, l-phenylephrine, to the right and reduced its maximum response but failed to alter the contraction to the partial agonist Sgd 101/75 (indanidine). Conversely, incubations with 2.0, 2.2 and 3.0 X 10(-8) M N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline invariably affected the contractions to Sgd 101/75 more than those to l-phenylephrine. In pithed rats, N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (1 or 2 mg/kg i.v., -30 min), as well as phenoxybenzamine (0.1 mg/kg i.v., -30 min), enhanced the effectiveness of nifedipine to inhibit the vasopressor responses to the alpha-1 adrenoceptor stimulant, cirazoline.(ABSTRACT TRUNCATED AT 250 WORDS)
在大鼠主动脉中，由去甲肾上腺素（3×10⁻⁷或10⁻⁵M）和钾离子（100 mM）引起的⁴⁵Ca²⁺内流，在预先存在苯氧苄胺（1或3×10⁻⁸M）5或10分钟的情况下，未受到显著影响。然而，这种处理显著减弱了由去甲肾上腺素（3×10⁻⁷或10⁻⁵M）介导的⁴⁵Ca²⁺外流。更高浓度的苯氧苄胺以及延长暴露时间，会损害由去甲肾上腺素引起的⁴⁵Ca²⁺内流，但不会影响由钾离子引起的⁴⁵Ca²⁺内流。相比之下，哌唑嗪（10⁻⁹ - 10⁻⁷M）以及N - 乙氧羰基 - 2 - 乙氧基 - 1,2 - 二氢喹啉（10⁻⁷或10⁻⁶M，作用5或10分钟），在拮抗由去甲肾上腺素引起的⁴⁵Ca²⁺内流和外流方面同样有效。将大鼠主动脉暴露于1.3×10⁻⁹M苯氧苄胺30分钟，会使对完全α₁肾上腺素能受体激动剂去氧肾上腺素的对数浓度 - 收缩反应曲线显著右移，并降低其最大反应，但不会改变对部分激动剂Sgd 101/75（茚达立啶）的收缩反应。相反，用2.0、2.2和3.0×10⁻⁸M的N - 乙氧羰基 - 2 - 乙氧基 - 1,2 - 二氢喹啉孵育，对Sgd 101/75收缩反应的影响总是比对去氧肾上腺素的影响更大。在脊髓麻醉大鼠中，N - 乙氧羰基 - 2 - 乙氧基 - 1,2 - 二氢喹啉（静脉注射1或2 mg/kg，-30分钟）以及苯氧苄胺（静脉注射0.1 mg/kg，-30分钟），增强了硝苯地平抑制对α₁肾上腺素能受体激动剂西拉唑啉的升压反应的效果。（摘要截断于250字）
