匹那地尔间接抑制豚鼠和兔肠系膜动脉中的神经肌肉传递。

Pinacidil inhibits neuromuscular transmission indirectly in the guinea-pig and rabbit mesenteric arteries.

作者信息

Nakashima M, Li Y, Seki N, Kuriyama H

机构信息

Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

出版信息

Br J Pharmacol. 1990 Nov;101(3):581-6. doi: 10.1111/j.1476-5381.1990.tb14124.x.

DOI:10.1111/j.1476-5381.1990.tb14124.x

PMID:1963799

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1917751/

Abstract

Effects of pinacidil were investigated on neuromuscular transmission in smooth muscle tissues of the rabbit and guinea-pig mesenteric arteries by both electrophysiological procedures and a bioassay of noradrenaline (NA) outflows. 2. Pinacidil (over 1 microM) hyperpolarized smooth muscle cell membranes in both tissues, in a concentration dependent manner. Pinacidil hyperpolarized and increased the ionic conductance of smooth muscle membrane more markedly in the rabbit mesenteric artery than in the guinea-pig. The hyperpolarization induced by pinacidil occurred in the presence or absence of endothelial cells and was blocked by glibenclamide. 3. Perivascular adrenergic nerve stimulation produced excitatory junction potentials (e.j.ps) and repetitive stimulation produced a facilitation of e.j.ps in both tissues. Pinacidil (over 1 microM) reduced the amplitude and the decay time of e.j.ps to a consistently greater extent in the rabbit mesenteric artery than in the guinea-pig. However, the facilitation process of e.j.ps was not modified following application of pinacidil (1 microM). The pinacidil-induced inhibition of e.j.ps was prevented by pretreatment with glibenclamide. 4. Pinacidil (30 microM) marginally increased the overflows of NA and its metabolite, 3,4-dihydroxyphenylglycol (DOPEG) released following repetitive perivascular nerve stimulations. 5. Pinacidil (10 microM) partly inhibited the voltage-dependent Ca channel, as estimated from the recovery process following removal of pinacidil, of action potentials evoked on e.j.ps. 6. It is concluded that pinacidil increases ionic conductance and hyperpolarizes smooth muscle cell membranes of the guinea-pig and rabbit mesenteric arteries and as a consequence, inhibits the neuromuscular transmission process occurring on adrenergic nerve stimulation with no reduction in the amount of released transmitter.

摘要

通过电生理方法和去甲肾上腺素（NA）流出生物测定法，研究了吡那地尔对兔和豚鼠肠系膜动脉平滑肌组织神经肌肉传递的影响。2. 吡那地尔（浓度超过1微摩尔）使两种组织中的平滑肌细胞膜超极化，且呈浓度依赖性。吡那地尔使兔肠系膜动脉平滑肌膜超极化并更显著地增加其离子电导，比在豚鼠中更明显。吡那地尔诱导的超极化在有或无内皮细胞存在时均发生，并被格列本脲阻断。3. 血管周围肾上腺素能神经刺激在两种组织中均产生兴奋性接头电位（e.j.ps），重复刺激产生e.j.ps的易化作用。吡那地尔（浓度超过1微摩尔）在兔肠系膜动脉中比在豚鼠中更持续地降低e.j.ps的幅度和衰减时间。然而，应用吡那地尔（1微摩尔）后，e.j.ps的易化过程未改变。吡那地尔诱导的e.j.ps抑制作用可被格列本脲预处理所预防。4. 吡那地尔（30微摩尔）略微增加了重复血管周围神经刺激后释放的NA及其代谢产物3,4 - 二羟基苯乙二醇（DOPEG）的流出量。5. 从去除吡那地尔后的恢复过程估计，吡那地尔（10微摩尔）部分抑制电压依赖性钙通道，该通道在e.j.ps诱发的动作电位中起作用。6. 得出结论，吡那地尔增加豚鼠和兔肠系膜动脉平滑肌细胞膜的离子电导并使其超极化，因此，抑制肾上腺素能神经刺激时发生的神经肌肉传递过程，而不减少释放递质的量。