Mishima S, Miyahara H, Suzuki H
Br J Pharmacol. 1984 Oct;83(2):537-47. doi: 10.1111/j.1476-5381.1984.tb16518.x.
Effects of alpha-adrenoceptor blockers (prazosin, yohimbine, phentolamine and phenoxybenzamine) on the outflow of noradrenaline (NA) and 3,4-dihydroxyphenylglycol (DOPEG) during perivascular nerve stimulation were observed in relation to electrical events in the rabbit mesenteric artery. Cocaine or imipramine increased the NA outflow and reduced the DOPEG outflow induced by nerve stimulation. In the absence of stimulation, cocaine and imipramine did not significantly modify the NA and DOPEG outflows. The alpha-adrenoceptor blockers we used enhanced the NA and DOPEG outflow during nerve stimulation, in a dose-dependent manner; the potency of the enhancement was higher for phentolamine and phenoxybenzamine than for prazosin and yohimbine. Higher concentrations (10(-5) M) of yohimbine reduced the NA and DOPEG outflows induced by nerve stimulation. Prazosin increased the DOPEG outflow in the absence of stimulation, and this effect was not inhibited by pretreatment with cocaine. Guanethidine increased the NA and DOPEG outflow in the absence of stimulation, and the NA outflow was reduced during nerve stimulation. These effects of guanethidine were prevented by pretreatment with cocaine or imipramine. Perivascular nerve stimulation evoked excitatory junction potentials (e.j.ps) and with high frequency stimulation, slow depolarization and spike potentials. Application of phentolamine, phenoxybenzamine or yohimbine enhanced, and of prazosin had no effect, on the amplitude of the e.j.p. Spike potentials were not affected by these alpha-adrenoceptor blockers. Slow depolarization ceased in the presence of prazosin, phentolamine or phenoxybenzamine, and was slightly inhibited by yohimbine. Guanethidine blocked all of these electrical responses induced by perivascular nerve stimulation. Application of prazosin, phentolamine or phenoxybenzamine did not alter the resting membrane potential of the smooth muscle cells. Depolarizations of smooth muscle membrane produced by exogenously applied NA were inhibited by prazosin, phentolamine or phenoxybenzamine. Yohimbine itself depolarized the membrane and the inhibitory effects on the NA-induced depolarization were weaker. We conclude that the smooth muscle membrane of the rabbit mesenteric artery possesses alpha 1-adrenoceptors. Increase in NA outflow by alpha-adrenoceptor antagonists during nerve stimulation was not always consistent with increase in e.j.p. amplitude, presumably due to involvement of actions other than alpha-adrenoceptor blockade with each of these antagonists.
观察了α-肾上腺素能受体阻滞剂（哌唑嗪、育亨宾、酚妥拉明和酚苄明）对兔肠系膜动脉血管周围神经刺激期间去甲肾上腺素（NA）和3,4-二羟基苯乙二醇（DOPEG）释放的影响，并将其与电活动相关联。可卡因或丙咪嗪增加了神经刺激诱导的NA释放，并减少了DOPEG释放。在无刺激情况下，可卡因和丙咪嗪对NA和DOPEG释放无明显影响。我们使用的α-肾上腺素能受体阻滞剂在神经刺激期间以剂量依赖性方式增强了NA和DOPEG释放；酚妥拉明和酚苄明的增强效力高于哌唑嗪和育亨宾。较高浓度（10⁻⁵ M）的育亨宾减少了神经刺激诱导的NA和DOPEG释放。哌唑嗪在无刺激情况下增加了DOPEG释放，且该作用不受可卡因预处理的抑制。胍乙啶在无刺激情况下增加了NA和DOPEG释放，而在神经刺激期间NA释放减少。可卡因或丙咪嗪预处理可阻止胍乙啶的这些作用。血管周围神经刺激诱发兴奋性接头电位（e.j.ps），高频刺激时出现缓慢去极化和锋电位。酚妥拉明﹑酚苄明或育亨宾可增强e.j.p.的幅度，而哌唑嗪无此作用。这些α-肾上腺素能受体阻滞剂对锋电位无影响。在哌唑嗪﹑酚妥拉明或酚苄明存在时，缓慢去极化停止，育亨宾对其有轻微抑制作用。胍乙啶阻断了血管周围神经刺激诱导的所有这些电反应。哌唑嗪﹑酚妥拉明或酚苄明的应用未改变平滑肌细胞的静息膜电位。外源性应用NA引起的平滑肌膜去极化受到哌唑嗪﹑酚妥拉明或酚苄明的抑制。育亨宾本身使膜去极化，且对NA诱导的去极化的抑制作用较弱。我们得出结论，兔肠系膜动脉的平滑肌膜具有α1-肾上腺素能受体。神经刺激期间α-肾上腺素能受体拮抗剂引起的NA释放增加并不总是与e.j.p.幅度增加一致，推测是由于这些拮抗剂除α-肾上腺素能受体阻断作用外还涉及其他作用。
