5-羟色胺对大鼠骶髓后连合神经元GABA(A)反应的增强作用

5-HT potentiation of the GABA(A) response in the rat sacral dorsal commissural neurones.

作者信息

Xu T L, Pang Z P, Li J S, Akaike N

机构信息

Department of Anatomy, K.K. Leung Brain Research Center, The Fourth Military Medical University, Xi'an, People's Republic of China.

出版信息

Br J Pharmacol. 1998 Jun;124(4):779-87. doi: 10.1038/sj.bjp.0701896.

DOI:10.1038/sj.bjp.0701896

PMID:9690871

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1565450/

Abstract

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 (IGABA) 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 IGABA while ketanserine blocked it. 1-Oleoyl-2-acetyl-glycerol (OAG) potentiated IGABA, and the effect of 5-HT on IGABA was occluded by OAG pretreatment. In the presence of chelerythrine, 5-HT failed to potentiate IGABA, suggesting that protein kinase C (PKC) is involved in the pathway through which the activation of the 5-HT2 receptor potentiates the IGABA. 4. The facilitatory effect of 5-HT on IGABA remained in the presence of BAPTA-AM. LiCl also had no effect on 5-HT-induced potentiation of IGABA. 5. H-89, genistein, okadaic acid and pervanadate all had no effects on 5-HT potentiation of IGABA. Pertussis toxin treatment for 6-8 h did not block the facilitatory effect of 5-HT on IGABA. 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.

摘要

在电压钳制条件下，采用制霉菌素穿孔膜片钳记录模式，研究了5-羟色胺（5-HT）对大鼠骶髓后连合核（SDCN）新鲜分离神经元γ-氨基丁酸A（GABA(A)）反应的调节作用。2. 5-HT增强了GABA诱导的Cl-电流（IGABA），但不影响IGABA的反转电位以及GABA与其受体的表观亲和力。3. α-甲基-5-HT模拟了5-HT对IGABA的增强作用，而酮色林则阻断了该作用。1-油酰-2-乙酰甘油（OAG）增强了IGABA，OAG预处理可阻断5-HT对IGABA的作用。在存在白屈菜红碱的情况下，5-HT无法增强IGABA，这表明蛋白激酶C（PKC）参与了5-HT2受体激活增强IGABA的信号通路。4. 在存在BAPTA-AM的情况下，5-HT对IGABA的促进作用依然存在。氯化锂对5-HT诱导的IGABA增强也没有影响。5. H-89、染料木黄酮、冈田酸和过钒酸盐对5-HT增强IGABA均无作用。百日咳毒素处理6-8小时并未阻断5-HT对IGABA的促进作用。6. 目前的结果表明，大鼠SDCN中的GABA(A)受体可在原位被5-HT调节，5-HT是参与伤害性感受脊髓上控制的主要神经递质之一，并且PKC对GABA(A)受体的磷酸化可能足以支持这种调节。这些结果也有力地支持了5-HT和GABA共同传递在脊髓中起重要作用的假说。