5-HT potentiation of the GABAA response in the rat sacral dorsal commissural neurones
5-HT potentiation of the GABAA response in the rat sacral dorsal commissural neurones
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DOI：
10.1038/sj.bjp.0701896
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发表时间：
1998-06-01
影响因子：
7.3
通讯作者：
Akaike, N
中科院分区：
文献类型：
--
作者：
Xu, TL;Pang, ZP;Akaike, N
1在电压钳条件下，采用制霉菌素穿孔膜片记录技术，观察5-羟色胺(5-HT)对大鼠骶髓后连合核(SDCN)神经元γ-氨基丁酸(GABA(A))反应的调制作用。2在不影响IGABA的翻转电位和GABA与其受体的表观亲和力的情况下，5-羟色胺增强GABA诱导的氯电流(I-GABA)。1-油酰基-2-乙酰甘油(OAG)增强IGAB(A)，5-羟色胺(5-HT)对i-GABA的影响可被OAG阻断。5-羟色胺不能增强I-GABA，提示蛋白激酶C(PKC)参与了5-HT2受体激活I-GABA的途径。4在BAPTA-AM存在下，5-HT对I(GABA)的易化作用仍然存在。5-羟色胺、染料木素、冈田酸和过钒酸盐均不影响5-羟色胺对i-GABA的增强作用。百日咳毒素处理6~8h不能阻断5-羟色胺对I-GABA的易化作用。本研究结果表明，5-羟色胺可原位调节大鼠SDCN内GABA(A)受体的活性，而PKC对GABA(A)受体的磷酸化可能足以支持这种调节。这一结果也有力地支持了5-羟色胺和GABA的共同传递在脊髓中起重要作用的假说。
1 The modulatory effect of 5-hydroxytryptamine (5-HT) on the gamma-aminobutyric acid(A) (GABA(A)) response was investigated in the neurones freshly dissociated from the rat sacral dorsal commissural nucleus (SDCN) using the nystatin perforated patch recording configuration under the voltage-clamp conditions.2 5-HT potentiated GABA-induced Cl- current (I-GABA) without affecting the reversal potential of IGABA and the apparent affinity of GABA to its receptor.3 alpha-Methyl-5-HT mimicked the potentiation effect of 5-HT on I-GABA while ketanserine blocked it. 1-Oleoyl-2-acetyl-glycerol (OAG) potentiated IGAB(A), and the effect of 5-HT on I-GABA was occluded by OAG pretreatment. In the presence of cheIerythrine, 5-HT failed to potentiate I-GABA, suggesting that protein kinase C (PKC) is involved in the pathway through which the activation of the 5-HT2 receptor potentiates the I-GABA.4 The facilitatory effect of 5-HT on I(GABA )remained in the presence of BAPTA-AM. LICl also had no effect on 5-HT-induced potentiation of I-GABA.5 H-89, genistein, okadaic acid and pervanadate all had no effects on 5-HT potentiation of I-GABA. Pertussis toxin treatment for 6-8 h did not block the facilitatory effect of 5-HT on I-GABA.6 The present results show that GABA(A) receptor in the rat SDCN could be modulated in situ by 5-HT, one of the major transmitters involved in the supraspinal control of nociception, and that the phosphorylation of GABA(A) receptor by PKC may be sufficient to support such modulation. The results also strongly support the hypothesis that the cotransmission by 5-HT and GABA has an important role in the spinal cord.