Shibata S, Satake N, Kurahashi K, Ohtsuka M
Department of Pharmacology, School of Medicine, University of Hawaii, Honolulu 96822.
J Cardiovasc Pharmacol. 1988 May;11(5):601-7. doi: 10.1097/00005344-198805000-00013.
The vasoinhibitory effect of FR 46171, a new pyridine alcohol derivative, on contractile responses to alpha-adrenoceptor agonists was examined in isolated rabbit aorta. FR 46171 (10(-8)-10(-5) M) inhibited the maximum contractile response to clonidine (CL) in a concentration-dependent manner, but it only inhibited the responses to low concentrations of norepinephrine (NE) and methoxamine (MO). In the aorta pretreated with phenoxybenzamine, however, FR 46171 at 10(-5) M inhibited the residual maximum response to NE and MO. FR 46171 at 10(-5) M only inhibited the response to KCl (20 mM). FR 46171 at 10(-6) and 10(-5) M also moderately inhibited the response to added Ca2+ in a Ca2+-free medium in K+-depolarized preparations. Nifedipine at 10(-6) M, by contrast, nearly abolished the responses to potassium or added Ca2+. In a Ca2+-free medium with EGTA, an addition of NE (10(-5) M), MO (10(-5) M), or CL (10(-5) M) induced a phasic contraction. The inhibitory effect of FR 46171 (10(-8)-10(-5) M) was much greater on the response to CL than that to NE or MO. In a Ca2+-free medium with low EGTA and nifedipine (10(-6) M) in the presence of an alpha-adrenoceptor agonist (NE, MO, or CL), an addition of Ca2+ (2 mM) induced a tonic contraction. FR 46171 (10(-9)-10(-5) M) inhibited the Ca2+ response, which is activated by the agonists, in a concentration-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)
在离体兔主动脉中研究了一种新型吡啶醇衍生物FR 46171对α-肾上腺素能受体激动剂收缩反应的血管抑制作用。FR 46171（10⁻⁸ - 10⁻⁵ M）以浓度依赖性方式抑制可乐定（CL）的最大收缩反应，但仅抑制对低浓度去甲肾上腺素（NE）和甲氧明（MO）的反应。然而，在用酚苄明预处理的主动脉中，10⁻⁵ M的FR 46171抑制了对NE和MO的残余最大反应。10⁻⁵ M的FR 46171仅抑制对氯化钾（20 mM）的反应。10⁻⁶和10⁻⁵ M的FR 46171也适度抑制了在钾离子去极化制剂的无钙培养基中对添加钙离子的反应。相比之下，10⁻⁶ M的硝苯地平几乎消除了对钾离子或添加钙离子的反应。在含有乙二醇双（2-氨基乙基醚）四乙酸（EGTA）的无钙培养基中，添加NE（10⁻⁵ M）、MO（10⁻⁵ M）或CL（10⁻⁵ M）会引起相性收缩。FR 46171（10⁻⁸ - 10⁻⁵ M）对CL反应的抑制作用比对NE或MO的抑制作用大得多。在含有低EGTA和硝苯地平（10⁻⁶ M）的无钙培养基中，在α-肾上腺素能受体激动剂（NE、MO或CL）存在下，添加钙离子（2 mM）会引起强直性收缩。FR 46171（10⁻⁹ - 10⁻⁵ M）以浓度依赖性方式抑制由激动剂激活的钙离子反应。（摘要截断于250字）
