Wu S Y, Dun S L, Wright M T, Chang J K, Dun N J
Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City 37614, USA.
Neuroscience. 1999 Mar;89(2):317-21. doi: 10.1016/s0306-4522(98)00570-3.
Endomorphin 1 and 2 are two tetrapeptides recently isolated from bovine as well as human brains and proposed to be the endogenous ligand for the mu-opiate receptor. Opioid compounds expressing mu-receptor preference are generally potent analgesics. The spinal cord dorsal horn is considered to be an important site for the processing of sensory information including pain. The discovery that endomorphins produced greater analgesia in mice upon intrathecal as compared to intracerebroventricular injections raises the possibility that dorsal horn neurons may represent the anatomic site upon which endomorphins exert their analgesic effects. We report here the detection of endomorphin 2-immunuoreactive fiber-like elements in superficial layers of the rat dorsal horn by immunohistochemical techniques. Whole-cell patch recordings from substantia gelatinosa neurons of cervical spinal cord slices revealed two conspicuous effects of exogenously applied endomorphin 1 and 2: (i) depression of excitatory postsynaptic potentials evoked by stimulation of dorsal root entry zone, and (ii) hyperpolarization of substantia gelatinosa neurons. These effects were reversed by the selective mu-opiate receptor antagonist beta-funaltrexamine. Collectively, the detection of endomorphin-like immunoreactivity in nerve fibers of the superficial layers and the inhibitory action of endomorphins on substantia gelatinosa neurons provide further support for a potential role of these two peptides in spinal nociception.
内吗啡肽1和2是最近从牛和人脑中分离出的两种四肽，被认为是μ阿片受体的内源性配体。表现出对μ受体偏好的阿片类化合物通常是强效镇痛药。脊髓背角被认为是处理包括疼痛在内的感觉信息的重要部位。与脑室内注射相比，鞘内注射内吗啡肽在小鼠中产生更强镇痛作用这一发现，增加了背角神经元可能是内吗啡肽发挥镇痛作用的解剖部位的可能性。我们在此报告用免疫组织化学技术在大鼠背角浅层检测到内吗啡肽2免疫反应性纤维样成分。对颈髓切片的胶状质神经元进行全细胞膜片钳记录，揭示了外源性应用内吗啡肽1和2的两种显著作用：（i）抑制刺激背根进入区诱发的兴奋性突触后电位，以及（ii）使胶状质神经元超极化。这些作用被选择性μ阿片受体拮抗剂β-芬太尼环唑逆转。总的来说，在浅层神经纤维中检测到内吗啡肽样免疫反应性以及内吗啡肽对胶状质神经元的抑制作用，为这两种肽在脊髓痛觉感受中的潜在作用提供了进一步支持。
