Ortiz-Miranda S I, Dayanithi G, Coccia V, Custer E E, Alphandery S, Mazuc E, Treistman S, Lemos J R
Department of Physiology and Program in Neuroscience and Neurobiology, University of Massachusetts Medical School, Worcester, MA, USA.
J Neuroendocrinol. 2003 Sep;15(9):888-94. doi: 10.1046/j.1365-2826.2003.01076.x.
The activation of opioid receptors in neurones of the central nervous system leads to a variety of effects including the modulation of diuresis and parturition, processes that are directly controlled by the hypothalamic-neurohypophysial system (HNS). The effects of mu-opioid receptor activation on peptide release, voltage-gated Ca2+ currents and intracellular calcium levels ([Ca2+]i) were studied in isolated nerve terminals of the HNS. The mu-receptor agonist, DAMGO ([d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin) inhibited high K+-induced peptide release in a dose-dependent manner, with oxytocin release being more sensitive to block than vasopressin release at all concentrations tested. The addition of the mu-receptor antagonist CTOP (d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr amide) was able to overcome the inhibitory effects of DAMGO. By contrast to previous results, voltage-gated Ca2+ currents were sensitive to blockage by DAMGO and this inhibition was also prevented by CTOP. Furthermore, [Ca2+]i measurements with Fura-2 corroborated the inhibition by DAMGO of calcium entry and its reversal by the micro -receptor antagonist in these nerve terminals. Thus, the decrease in neuropeptide release, particularly for oxytocin, induced by the activation of mu-opioid receptors in neurohypophysial terminals is mediated, at least in part, by a corresponding decrease in Ca2+ entry due to the inhibition of voltage-gated Ca2+ channels.
中枢神经系统神经元中阿片受体的激活会导致多种效应，包括对利尿和分娩的调节，而这些过程直接受下丘脑 - 神经垂体系统（HNS）控制。在HNS的离体神经末梢中研究了μ - 阿片受体激活对肽释放、电压门控Ca2 +电流和细胞内钙水平（[Ca2 +]i）的影响。μ - 受体激动剂DAMGO（[d - Ala2，N - Me - Phe4，Gly5 - ol] - 脑啡肽）以剂量依赖性方式抑制高K +诱导的肽释放，在所有测试浓度下，催产素释放比血管加压素释放对阻断更敏感。添加μ - 受体拮抗剂CTOP（d - Phe - Cys - Tyr - d - Trp - Orn - Thr - Pen - Thr酰胺）能够克服DAMGO的抑制作用。与先前的结果相反，电压门控Ca2 +电流对DAMGO的阻断敏感，并且这种抑制也被CTOP阻止。此外，用Fura - 2测量[Ca2 +]i证实了DAMGO对这些神经末梢中钙内流的抑制作用以及微受体拮抗剂对其的逆转作用。因此，神经垂体末梢中μ - 阿片受体激活诱导的神经肽释放减少，特别是催产素的释放减少，至少部分是由于电压门控Ca2 +通道的抑制导致Ca2 +内流相应减少所介导的。
