没有证据表明大鼠门静脉对去氧肾上腺素、5-羟色胺或乙酰甲胆碱的初始快速收缩反应和继发的缓慢收缩反应存在差异拮抗作用。

No evidence for the differential antagonism of the initial fast and secondary slow contractile responses of the rat portal vein to phenylephrine, 5-hydroxytryptamine or methacholine.

作者信息

Doggrell S A

机构信息

Department of Pharmacology, School of Medicine, University of Auckland, New Zealand.

出版信息

J Auton Pharmacol. 1988 Jun;8(2):69-78. doi: 10.1111/j.1474-8673.1988.tb00171.x.

DOI:10.1111/j.1474-8673.1988.tb00171.x

PMID:2902098

Abstract

The present study was to ascertain whether drugs cause differential antagonism of the initial fast and secondary slow contractile responses to phenylephrine, 5-HT and methacholine of the rat portal vein. 2. Cocaine (5 x 10(-6) M) had no effect on the responses to methacholine. Cocaine potentiated the initial fast but not the secondary slow responses to phenylephrine suggesting that neuronal uptake limits the initial fast but not the secondary slow response to phenylephrine. Cocaine reduced the maximal responses to 5-HT suggesting that the responses to high concentrations of 5-HT are due, in part, to the release of noradrenaline. 3. In the presence of cocaine, idazoxan had no effect on responses to phenylephrine or 5-HT and prazosin had no effect on responses to 5-HT. Prazosin (3 x 10(-9)-10(-8) M) inhibited the responses to phenylephrine causing similar parallel rightward shifts of the concentration-response curves to the initial fast and secondary slow responses. 4. In the presence of cocaine, mianserin (10(-9)-10(-8) M), cyproheptadine, (10(-10)-10(-9) M), methysergide (10(-8) M), ketanserin (10(-10)-10(-9) M) and Ly 53857 (at 10(-9)-10(-8) M) had similar inhibitory effects on the initial fast and secondary slow responses to 5-HT, namely a parallel rightward displacement of the concentration-response curves. 5. Atropine (less than or equal to 10(-7) M) and pirenzepine less than or equal to 10(-6) M) had no effect on the responses to phenylephrine and 5-HT, but caused similar parallel rightward shifts of the concentration-response curves to both responses to methacholine. 6. The results of this study provide no evidence for differential antagonism of the initial fast and secondary slow responses of the rat portal vein to phenylephrine, 5-HT or methacholine.

摘要

本研究旨在确定药物是否会对大鼠门静脉对去氧肾上腺素、5-羟色胺和乙酰甲胆碱的初始快速收缩反应及继发性缓慢收缩反应产生不同的拮抗作用。2. 可卡因（5×10⁻⁶ M）对乙酰甲胆碱的反应无影响。可卡因增强了对去氧肾上腺素的初始快速反应，但未增强继发性缓慢反应，这表明神经元摄取限制了对去氧肾上腺素的初始快速反应而非继发性缓慢反应。可卡因降低了对5-羟色胺的最大反应，这表明对高浓度5-羟色胺的反应部分归因于去甲肾上腺素的释放。3. 在存在可卡因的情况下，咪唑克生对去氧肾上腺素或5-羟色胺的反应无影响，哌唑嗪对5-羟色胺的反应无影响。哌唑嗪（3×10⁻⁹ - 10⁻⁸ M）抑制了对去氧肾上腺素的反应，使浓度-反应曲线对初始快速反应和继发性缓慢反应产生类似的平行右移。4. 在存在可卡因的情况下，米安色林（10⁻⁹ - 10⁻⁸ M）、赛庚啶（10⁻¹⁰ - 10⁻⁹ M）、美西麦角（10⁻⁸ M）、酮色林（10⁻¹⁰ - 10⁻⁹ M）和Ly 53857（10⁻⁹ - 10⁻⁸ M）对5-羟色胺的初始快速反应和继发性缓慢反应具有类似的抑制作用，即浓度-反应曲线平行右移。5. 阿托品（≤10⁻⁷ M）和哌仑西平（≤10⁻⁶ M）对去氧肾上腺素和5-羟色胺的反应无影响，但使浓度-反应曲线对乙酰甲胆碱的两种反应产生类似的平行右移。6. 本研究结果未提供证据表明大鼠门静脉对去氧肾上腺素、5-羟色胺或乙酰甲胆碱的初始快速反应和继发性缓慢反应存在不同的拮抗作用。