Innis R B, Aghajanian G K
Department of Psychiatry, Yale University School of Medicine, New Haven, CT.
Eur J Pharmacol. 1987 Nov 10;143(2):195-204. doi: 10.1016/0014-2999(87)90533-4.
To examine the role of guanine nucleotide binding (G) proteins in receptor-mediated inhibition of serotonin (5-HT) neurons, we intracerebrally injected pertussis toxin (0.5-1.0 microgram) into rat midbrain in a region immediately rostral to the dorsal raphe nucleus. The baseline firing rate of extracellularly recorded 5-HT neurons was not significantly affected by pertussis toxin treatment. However, in comparison to saline-injected controls, pertussis toxin-injected animals showed markedly blunted sensitivity to agonists that act at 5-HT autoreceptors (isapirone, 5-HT and LSD) and to baclofen, a GABAB agonist. This pertussis toxin-induced blunting of sensitivity was demonstrated in vivo (with intravenous and iontophoretic application of drugs) and in vitro in the dorsal raphe brain slice preparation. The sensitivity of iontophoretically applied GABA itself was not significantly decreased with pertussis toxin treatment, consistent with evidence that GABA administered in this manner acts on dorsal raphe cells mainly through GABAA receptors. Our data provide strong evidence for the role of a pertussis toxin substrate(s) (presumably a G protein(s] in mediating the inhibition induced by the autoreceptor and GABAB receptor on 5-HT neurons in rat dorsal raphe nucleus.
为研究鸟嘌呤核苷酸结合（G）蛋白在受体介导的5-羟色胺（5-HT）能神经元抑制中的作用，我们将百日咳毒素（0.5 - 1.0微克）脑内注射到大鼠中脑紧靠中缝背核嘴侧的区域。细胞外记录的5-HT能神经元的基础放电频率未受百日咳毒素处理的显著影响。然而，与注射生理盐水的对照相比，注射百日咳毒素的动物对作用于5-HT自身受体的激动剂（伊沙匹隆、5-HT和麦角酸二乙胺）以及GABAB激动剂巴氯芬的敏感性明显降低。这种百日咳毒素诱导的敏感性降低在体内（通过静脉内和离子导入法给药）以及中缝背脑片制备的体外实验中均得到证实。离子导入法应用的GABA自身的敏感性在百日咳毒素处理后未显著降低，这与以这种方式给予的GABA主要通过GABAA受体作用于中缝背核细胞的证据一致。我们的数据为百日咳毒素底物（可能是一种G蛋白）在介导自身受体和GABAB受体对大鼠中缝背核5-HT能神经元的抑制作用中的作用提供了有力证据。
