Mallard N, Marshall R, Sithers A, Spriggs B
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Heath Park, Cardiff, South Glamorgan, UK.
Eur J Pharmacol. 1992 Sep 10;220(1):1-10. doi: 10.1016/0014-2999(92)90004-n.
The effects of the putative P2 purinoceptor antagonist suramin on contractile responses of the rat isolated vas deferens to electrical field stimulation and exogenously applied drugs (alpha,beta-methylene ATP and noradrenaline) were investigated. Suramin was devoid of agonist activity in the rat vas deferens. The response of the vas deferens to single pulse field stimulation was characteristically biphasic with a large first component peaking between 260-300 ms after the stimulus followed by a second smaller component peaking at about 650 ms post-stimulus. Suramin (100 nM-1 mM) selectively impaired the first, purinergic phase of the response to single pulse field stimulation but was without effect on the second, noradrenergic component. The response of the vas deferens to trains of electrical field stimuli (10 Hz for 10 s) was also biphasic. Suramin (1 microM-1 mM) reduced the first (less than 1 s) phase of the response by 30%, the second (greater than 5 s) plateau phase by 50% and inhibited the intermediate (2-4 s) phase by 80%. Dose-contact periods of 20 or 30 min respectively were sufficient to achieve equilibration of the inhibitory effects of suramin against the responses to single pulse field stimulation or trains of pulses. Following 30 min incubation with 1 mM suramin, the remaining first and second phase components of the response to trains of pulses were impaired and subsequently abolished by the alpha 1-adrenoceptor antagonist WB4101 establishing their noradrenergic origin. Suramin (300 microM) abolished responses of the vas deferens to alpha,beta-methylene ATP but was without effect on those to noradrenaline. Suramin (30 microM) induced a rightward shift in the concentration-response relationship to alpha,beta-methylene ATP that was associated with a significant 40% increase in the maximum response, but did not modify responses to noradrenaline. The inhibitory effects of suramin (3-300 microM) on responses of the vas deferens to approximate EC50 concentrations of alpha,beta-methylene ATP were reversible on repeated washout for 40-60 min. These results reveal suramin to be a useful pharmacological tool for the study of purinergic neurotransmission in rodent vasa deferentia.
研究了假定的P2嘌呤受体拮抗剂苏拉明对大鼠离体输精管电场刺激及外源性给药（α,β-亚甲基ATP和去甲肾上腺素）收缩反应的影响。苏拉明在大鼠输精管中无激动剂活性。输精管对单脉冲电场刺激的反应典型地呈双相性，第一个大的成分在刺激后260 - 300毫秒达到峰值，随后第二个较小的成分在刺激后约650毫秒达到峰值。苏拉明（100 nM - 1 mM）选择性地损害了对单脉冲电场刺激反应的第一个嘌呤能相，但对第二个去甲肾上腺素能成分无影响。输精管对电场刺激串（10 Hz，持续10秒）的反应也是双相性的。苏拉明（1 μM - 1 mM）使反应的第一个（小于1秒）相降低30%，第二个（大于5秒）平台相降低50%，并抑制中间（2 - 4秒）相80%。分别20或30分钟的剂量接触期足以使苏拉明对单脉冲电场刺激或脉冲串反应的抑制作用达到平衡。与1 mM苏拉明孵育30分钟后，对脉冲串反应的剩余第一和第二相成分受到损害，随后被α1 -肾上腺素能拮抗剂WB4101消除，证实了它们的去甲肾上腺素能起源。苏拉明（300 μM）消除了输精管对α,β-亚甲基ATP的反应，但对去甲肾上腺素的反应无影响。苏拉明（30 μM）使对α,β-亚甲基ATP的浓度-反应关系向右移位，这与最大反应显著增加40%相关，但不改变对去甲肾上腺素的反应。苏拉明（3 - 300 μM）对输精管对近似EC50浓度的α,β-亚甲基ATP反应的抑制作用在反复洗脱40 - 60分钟后是可逆的。这些结果表明苏拉明是研究啮齿动物输精管中嘌呤能神经传递的有用药理学工具。
