Gonzalez-Alvear G M, Thompson-Montgomery D, Deben S E, Werling L L
Department of Pharmacology, George Washington University Medical Center, Washington, D.C. 20037, USA.
J Neurochem. 1995 Dec;65(6):2509-16. doi: 10.1046/j.1471-4159.1995.65062509.x.
Autoradiographic studies have shown that sigma receptors are enriched in the locus coeruleus, the origin of noradrenergic projections to the cerebellum, as well as in the Purkinje, molecular, and granular layers and the interpositus cerebellar nucleus of the cerebellum itself. In contrast, the cerebellum is relatively poor in phencyclidine (PCP) binding sites, which have been historically confused with sigma sites. The high ratio of sigma to PCP receptors in cerebellum is advantageous for discriminating sigma-mediated physiological effects. sigma agonists and antagonists have been shown to regulate N-methyl-D-aspartate (NMDA)-stimulated norepinephrine release in hippocampus, which is innervated by locus coeruleus projections. We now report that sigma drugs also regulate norepinephrine release from cerebellum. In contrast to findings in the hippocampus, where regulation is via sigma 1 and sigma 2 receptors, sigma-mediated regulation in cerebellum seems to be primarily via sigma 1 receptors. In radioligand binding studies, we find that sigma receptors primarily of the sigma 1 type are present in the cerebellum. We further report that binding to sigma receptors in cerebellum is not affected by the addition of NMDA or glycine or by the presence of NMDA antagonists, suggesting that sigma receptors are not located within the NMDA-operated cation channel in this brain region.
放射自显影研究表明，σ受体在蓝斑核中高度富集，蓝斑核是去甲肾上腺素能投射到小脑的起源部位，同时也存在于小脑本身的浦肯野细胞层、分子层、颗粒层以及小脑间位核中。相比之下，小脑中苯环己哌啶（PCP）结合位点相对较少，历史上PCP结合位点曾与σ位点混淆。小脑中σ受体与PCP受体的高比例有利于区分σ介导的生理效应。已有研究表明，σ激动剂和拮抗剂可调节蓝斑核投射支配的海马体中N-甲基-D-天冬氨酸（NMDA）刺激的去甲肾上腺素释放。我们现在报告，σ药物也可调节小脑去甲肾上腺素的释放。与海马体中的发现不同，海马体中的调节是通过σ1和σ2受体进行的，而小脑中σ介导的调节似乎主要通过σ1受体。在放射性配体结合研究中，我们发现小脑中主要存在σ1型的σ受体。我们进一步报告，向小脑中添加NMDA或甘氨酸，或存在NMDA拮抗剂，均不会影响与σ受体的结合，这表明在该脑区中，σ受体并不位于NMDA操纵的阳离子通道内。
