Lau W A, Ventura S, Jiang Q, Pennefather J N
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Eur J Pharmacol. 1995 Jan 5;272(1):31-8. doi: 10.1016/0014-2999(94)00624-g.
Experiments were conducted to elucidate the mechanisms of action of endothelins in facilitating neurotransmission to the rat isolated vas deferens. Endothelin-1 and endothelin-3 potentiated field stimulation-induced contractions and those evoked by ATP and alpha, beta-methylene ATP. Responses to noradrenaline were unaffected. The C-terminal hexapeptide, endothelin-(16-21) was without effect on neurotransmission. The facilitation by endothelin-1 of responses to trains of stimulation (10 Hz for 10 s) was absent in the presence of the P2-purinoceptor antagonist, suramin, in concentrations which antagonised the contractile effects of alpha, beta-methylene ATP, but not those of noradrenaline. Suramin did not affect 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)- phenyl]-3-pyridine carboxylic acid methyl ester (Bay K 8644)-induced potentiation of contractions in response to field stimulation. These results support the hypothesis that endothelin-induced facilitation of sympathetic neurotransmission to the vas deferens is due to potentiation of the postjunctional effects of the co-transmitter, ATP, acting at P2X-purinoceptors, and indicate that this effect is mediated through actions at endothelin receptors that are not of the ETB-subtype.
开展实验以阐明内皮素促进神经传递至大鼠离体输精管的作用机制。内皮素-1和内皮素-3增强了电场刺激诱导的收缩以及由ATP和α,β-亚甲基ATP诱发的收缩。对去甲肾上腺素的反应未受影响。C末端六肽，内皮素-(16 - 21)对神经传递无作用。在存在P2嘌呤受体拮抗剂苏拉明的情况下，内皮素-1对串刺激（10Hz，持续10秒）反应的促进作用消失，苏拉明的浓度能拮抗α,β-亚甲基ATP的收缩效应，但不影响去甲肾上腺素的收缩效应。苏拉明不影响1,4 - 二氢-2,6 - 二甲基-5 - 硝基-4 - [2 - (三氟甲基)-苯基]-3 - 吡啶羧酸甲酯（Bay K 8644）诱导的对电场刺激反应的收缩增强作用。这些结果支持以下假说：内皮素诱导的对输精管交感神经传递的促进作用是由于共同递质ATP作用于P2X嘌呤受体的接头后效应增强，并且表明这种效应是通过作用于非ETB亚型的内皮素受体介导的。
