Kullak A, Donoso M V, Huidobro-Toro J P
Eur J Pharmacol. 1987 Mar 31;135(3):297-305. doi: 10.1016/0014-2999(87)90678-9.
To investigate whether the neurotensin-induced relaxation of the rat duodenum and ileum is dependent on the external concentration of calcium, the effect of the neuropeptide was studied in isolated intestinal segments superfused with Tyrode solution containing no calcium, 1 or 2.5 mM Ca2+. The neurotensin-induced intestinal relaxation was reduced when the extracellular calcium concentration was lowered. In addition, the inhibitory effect of neurotensin was cancelled when the tissues were incubated in the presence of diltiazem, methoxyverapamil or nifedipine. BAY K-8644, a structural analog of nifedipine that functions as an agonist of the calcium channel, potentiated the neurotensin-induced smooth muscle relaxation. The facilitatory effect of BAY K-8644 was antagonized by nifedipine, indicating competition between the 2 dihydropyridines. Apamin, the K+ channel blocker, antagonized the neurotensin-induced visceral relaxation, displacing the concentration-response curve of the peptide to the right. Furthermore, apamin also blocked the effect of neurotensin when the neuropeptide was assayed in the presence of BAY K-8644. It is concluded that the smooth muscle relaxation induced by neurotensin is dependent on external calcium, suggesting that the activation of the neuropeptide receptor causes an influx of calcium which leads to the opening of K+ channels before smooth muscle relaxation is triggered.
为研究神经降压素诱导的大鼠十二指肠和回肠舒张是否依赖于细胞外钙浓度，我们在不含钙、含1或2.5 mM Ca²⁺的台氏液灌流的离体肠段中研究了该神经肽的作用。细胞外钙浓度降低时，神经降压素诱导的肠舒张减弱。此外，当组织在地尔硫卓、甲氧维拉帕米或硝苯地平存在的情况下孵育时，神经降压素的抑制作用被消除。BAY K - 8644是硝苯地平的结构类似物，作为钙通道激动剂，可增强神经降压素诱导的平滑肌舒张。硝苯地平可拮抗BAY K - 8644的促进作用，表明这两种二氢吡啶之间存在竞争。钾通道阻滞剂蜂毒明肽可拮抗神经降压素诱导的内脏舒张，使该肽的浓度 - 反应曲线右移。此外，当在BAY K - 8644存在的情况下检测神经肽时，蜂毒明肽也可阻断神经降压素的作用。结论是神经降压素诱导的平滑肌舒张依赖于细胞外钙，提示神经肽受体的激活导致钙内流，在触发平滑肌舒张之前导致钾通道开放。
