5-HT3-like receptors in the rat medial prefrontal cortex: Further pharmacological characterization
5-HT3-like receptors in the rat medial prefrontal cortex: Further pharmacological characterization
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DOI：
10.1016/0006-8993(96)00529-x
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发表时间：
1996-09-09
期刊：
影响因子：
2.9
通讯作者：
Wang, RY
中科院分区：
文献类型：
--
作者：
Edwards, E;Hampton, E;Wang, RY
该研究的目的是结合生化和电生理学方法，进一步表征大鼠内侧前额皮质 (mPFC) 中 5-羟色胺 (5-HT)(3) 样受体的药理学特性。苯基双胍 (PEG) 和三种氯化衍生物，邻氯-PBG (oCPBG)、间-氯-PBG (mCPBG) 和对-氯-PBG (pCPBG)，剂量依赖性地刺激额扣带皮层切片中的磷酸离子醇 (PI) 周转。 PBG 的所有三种氯代异构体在刺激 PI 周转方面都是等效的。 SR 57227A（(4-氨基)-(6-氯-2-吡啶基) L-哌啶盐酸盐，一种对外周和中枢 5-HT3 受体具有高亲和力和选择性的新型化合物）剂量依赖性地刺激额扣带皮层切片中的 PI 周转。与 5-HT 相比，PI 测定中测试的所有 5-HT3 受体激动剂的效力排序为：5-HT > 2-Me-5-HT > SR57227A > PBG = mCPBG = oCPBG = mCPBG。 5-HT 和 5-HT 受体激动剂以电流（剂量）依赖性方式抑制自发活性和谷氨酸激活的静止 mPFC 细胞的放电率。这些化合物的有效性排序为：5-HT > SR57227A = 2-Me-5-HT = mCPBG = oCPBG = pCPBG = PBG。与外周或培养细胞系中 5-HT3 受体的作用不同，D-筒箭毒碱氯化物在阻断 2-Me-5-HT、γ-氨基丁酸和多巴胺的抑制作用方面似乎是非特异性的。我们的结果综合支持这样的观点：mPFC 中 5-HT3 样受体的药理学特性与位于外周组织和培养细胞系中的受体不同。
The aim of the study was to further characterize the pharmacological properties of 5-hydroxytryptamine (5-HT)(3)-like receptors in the rat medial prefrontal cortex (mPFC) using combinations of biochemical and electrophysiological approaches. Phenylbiguanide (PEG) and three chlorinated derivatives, ortho-chloro-PBG (oCPBG), meta-chloro-PBG (mCPBG) and para-chloro-PBG (pCPBG), dose-dependently stimulated phosphoionositide (PI) turnover in fronto-cingulate cortical slices. All three chloro-isomers of PBG were equipotent in stimulating PI turnover. SR 57227A ((4-amino)-(6-chloro-2-pyridyl) L-piperidine hydrochloride, a novel compound with high affinity and selectivity for peripheral and central 5-HT3 receptors) dose-dependently stimulated PI turnover in fronto-cingulate cortical slices. The rank order of potency of all the 5-HT3 receptor agonists tested in the PI assay as compared to 5-HT was: 5-HT > 2-Me-5-HT > SR57227A > PBG = mCPBG = oCPBG = mCPBG. 5-HT and 5-HT receptor agonists depressed the firing rate of both spontaneously active and glutamate-activated quiescent mPFC cells in a current (dose)-dependent fashion. The rank order of effectiveness of these compounds was: 5-HT > SR57227A = 2-Me-5-HT = mCPBG = oCPBG = pCPBG = PBG. Unlike its action on the 5-HT3 receptors in the periphery or cultured cell Lines, D-tubocurarine chloride appears to be non-specific in blocking the depressant action of 2-Me-5-HT, gamma-aminobutyric acid and dopamine. Our results combined support the view that the pharmacological properties of 5-HT3-like receptors in the mPFC are not identical to those located in peripheral tissues and in cultured cell lines.