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5‐HT potentiation of the GABA A response in the rat sacral dorsal commissural neurones
Author(s) -
Xu TianLe,
Pang ZhiPing,
Li JiShuo,
Akaike Norio
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701896
Subject(s) - long term potentiation , chemistry , protein kinase c , gabaa receptor , gamma aminobutyric acid , chelerythrine , pharmacology , receptor , medicine , biochemistry , biology , phosphorylation
The modulatory effect of 5‐hydroxytryptamine (5‐HT) on the γ‐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. 5‐HT potentiated GABA‐induced Cl − current ( I GABA ) without affecting the reversal potential of I GABA and the apparent affinity of GABA to its receptor. α‐Methyl‐5‐HT mimicked the potentiation effect of 5‐HT on I GABA while ketanserine blocked it. 1‐Oleoyl‐2‐acetyl‐glycerol (OAG) potentiated I GABA , and the effect of 5‐HT on I GABA was occluded by OAG pretreatment. In the presence of chelerythrine, 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‐HT 2 receptor potentiates the I GABA . 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 . 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 . 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.