Substance P depresses GABA-activated currents in cultured hippocampal pyramidal neurons of rats

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Author:
XIONG Shun-Hua()
LI ZHI-WANG()
FAN You-Zhen()
Wang Ming-jiang()
WEI Jin-bo()
Journal Title:
ACTA PHYSIOLOGICA SINICA
Issue:
Volume 53, Issue 02, 2001
DOI:
Key Word:

Abstract: The purpose of the present study was to explore whether substance P (SP) modulates the response mediated by GABAA receptors. Experiments were carried out on cultured hippocampal pyramidal neurons of rats. GABA-activated inward currents were recorded using the whole-cell-patch-clamp techique. The majority of the neurons examined (66/92, 72%) were sensitive to both GABA and SP. When the neurons were treated with SP prior to application of GABA, the GABA-activated current (IGABA) was inhibited markedly, which was concentration-dependent and could be blocked by spantide, an NK1 receptor antagonist. With 10-8, 10-7, 10-6 and 10-5 mol/L SP, IGABA was inhibited by 18%, 24.8%, 25.9% and 28% respectively. Intracellular application of H7, a potent inhibitor of PKC, abolished inhibition of IGABA by SP, suggesting that the inhibition of IGABA by SP may be a result of intracellular phosphorylation of the GABAA receptor.

  • [1]Bormann J. The ‘ABC’ of GABA receptors. Trends Pharmacol Sci, 2000, 21:16~19.
  • [2]Wei JY (魏继业), Wang HL (王海龙), Yang XL (杨雄里) et al. Novel GABAC receptors. Prog Physiol Sci (生理科学进展), 1995, 26:7~11 (Chinese).
  • [3]Sieghart W. GABAA receptor: ligand-gated Cl- ion channels modulated by multiple drug-binding site. Trends Pharmacol Sci, 1992, 13:446~451.
  • [4]Stephenson FA. The GABAA receptor. Biochem J, 1995, 310:1~9.
  • [5]Wu XP (吴晓平), Li ZW (李之望), Fan YZ (樊友珍). Inhibitory effect of SP on GABA-activated currents in freshly isolated rat DRG neurons. Acta Physiol Sin (生理学报), 1994, 46(6):586~590 (Chinese, English abstract).
  • [6]Si JQ (司军强), Li ZW (李之望), Fan YZ (樊友珍).Subtypes of glutamate receptor and their distribution in the somatic membrane of neurons freshly isolated from rat DRG. Acta Physiol Sin (生理学报), 1996, 48(1):23~30 (Chinese, English abstract).
  • [7]Guan BC (关兵才), Li ZW (李之望), Zhou XP (周小萍).Modulatory effects of substance P on the membrane responses mediated by GABAA and GABAB receptors in DRG neurons. Acta Physiol Sin (生理学报), 1994, 46(4):441~450 (Chinese, English abstract).
  • [8]Yamada K, Akasu T. Substance P suppresses GABAA receptor function via protein kinase in primary sensory neurones of bullfrogs. J Physiol, 1996, 496:439~449.
  • [9]Li Q (李琴), Wang QW (王钦文), Li ZW (李之望). Inhibition by SKF38393 of GABA-activated currents in rat DRG neurons. Acta Physiol Sin (生理学报), 1998, 50(3):280~288 (Chinese, English abstract).
  • [10]Hu HZ, Li ZW. Modulation by adenosine of GABA-activated current in rat dorsal root ganglion neurons. J Physiol, 1997, 501:67~75.
  • [11]Otsuka M, Yoshioka K.Neurotransmitter functions of mammalian tachykinins. Physiol Rev, 1993, 73:229~308.
  • [12]Acsady L, Katona I, Gulyas AI et al. Immunostaining for substance P receptor labels GABAergic cells distinct termination patterns in the hippocampus. J Comp Neurol, 1997, 378(3):320~336.
  • [13]Ye JH, Liu PL, Wu WH et al. Cocaine depresses GABAA current of hippocampal neurons.Brain Res, 1997, 770:169~175.
  • [14]Ye JH, Ren J, Krnjevic K et al. Cocaine and lidocaine have additive inhibitory effects on the GABAA current of acutely dissocaited hippocampal pyramidal neurons. Brain Res, 1999, 821:26~32.
  • [15]Krishek BJ, Xie X, Blackstone C et al. Regulation of GABAA receptor function by protein kinase C phosphorylation. Neuron, 1994, 12:1081~1095.
  • [16]Mclean H, Caillard O, Ben-Ari Y. Bi-directional plasticity expressed by GABAergic synapses in the neonatal rat hippocampus. J Physiol, 1996, 496:471~477.
  • [17]Akhondzadeh S, stone TW. Induction of a novel form of hippocampal long-term depression by muscimol:involvement of GABAA but not glutamate receptors. Br J Pharmacol, 1995, 115:527~533.
  • [18]Caillard O, Ben-Ari Y, Gaiarsa JL. Long-term potentiation of GABAergic synaptic transmission in neonatal rat hippocampus. J Physiol, 1999, 518:109~119.
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