Release of [H-3]dopamine from guinea pig striatal slices is modulated by sigma(1) receptor agonists
Release of [H-3]dopamine from guinea pig striatal slices is modulated by sigma(1) receptor agonists
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DOI：
10.1007/pl00005076
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发表时间：
1997-10-01
影响因子：
3.6
通讯作者：
Werling, LL
中科院分区：
文献类型：
--
作者：
Gonzalez, GM;Werling, LL
Sigma受体存在于人类、非人类灵长类动物和啮齿类动物的大脑运动和边缘区域。最广泛的配体与sigma受体结合的药理学研究利用了豚鼠的脑组织，在那里已经鉴定出两种亚型的sigma受体，命名为sigma(1)和sigma(2)。Sigma受体的功能作用还很少被描述。它们在豚鼠纹状体的位置，黑质发出的多巴胺能投射的终末区域，表明这个组织将是检查sigma受体激活的生理特性的合理选择。我们发现Sigma(1)受体激动剂以浓度依赖的方式抑制N-甲基-D-天冬氨酸刺激的豚鼠纹状体脑片多巴胺的释放。选择性Sigma(1)受体拮抗剂和非亚型选择性Sigma受体拮抗剂均可逆转Sigma(1)受体激动剂的抑制作用。激动剂通过Sigma受体而不是Sigma(2)受体抑制儿茶酚胺的刺激释放的能力似乎是豚鼠纹状体的独特特征。我们先前已经报道，在大鼠纹状体和海马区，以及在豚鼠伏核、前额叶皮质和海马区，任何一种sigma受体亚型的激活都会抑制这种释放。苯环利定受体激动剂地佐西平也能抑制豚鼠纹状体[H-3]多巴胺的刺激释放，但这种抑制作用不能被Sigma受体拮抗剂逆转。因此，Sigma受体激动剂产生的抑制作用不是通过N-甲基-D-天冬氨酸操作的阳离子通道内的苯环利定结合位点来介导的。我们的发现支持这样一种假设，即Sigma受体激活提供了一种调节纹状体释放多巴胺的机制，而豚鼠的纹状体组织似乎是表征Sigma(1)受体介导的效应的合适模型。
Sigma receptors are found in motor and limbic areas in the brains of humans, non-human primates, and rodents. The most extensive pharmacological studies of ligand binding to sigma receptors have utilized brain tissue from guinea pigs, where two subtypes of sigma receptor, designated sigma(1) and sigma(2), have been identified. Few functional roles for sigma receptors have been described. Their location in guinea pig striatum, a terminal field of dopaminergic projections arising from the substantia nigra, suggested that this tissue would be a logical choice in which to examine physiological properties of sigma receptor activation. We found that sigma(1) receptor agonists inhibited N-methyl-D-aspartate-stimulated [H-3]dopamine release from guinea pig striatal slices in a concentration-dependent manner. The inhibition by sigma(1) receptor agonists was reversed by a selective sigma(1) receptor antagonist, as well as by a non-subtype-selective sigma receptor antagonist. The ability of agonists working through sigma, receptors, but not through sigma(2) receptors, to inhibit the stimulated release of catecholamines appears to be a unique characteristic of guinea pig striatum. We have previously reported that in rat striatum and hippocampus, as well as in guinea pig nucleus accumbens, prefrontal cortex, and hippocampus, activation of either sigma receptor subtype inhibits such release. Stimulated release of [H-3]dopamine from guinea pig striatum was also inhibited by the phencyclidine receptor agonist dizocilpine, but this inhibition was not reversed by the sigma receptor antagonists. Therefore, the inhibition produced by sigma receptor agonists was not mediated via the phencyclidine binding site within the N-methyl-D-aspartate-operated cation channel. Our findings support the hypothesis that sigma receptor activation provides a mechanism of modulating dopamine release from striatum, and that striatal tissue from guinea pigs appears to be an appropriate model for characterizing sigma(1) receptor-mediated effects.