ドーパミン作動性反回入力と興奮性および抑制性入力応答との細胞内クロストーク

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To investigate the intracellular cross-talk between the receptor for inhibitory amino acid and the monoamine receptor, the following experiments have been performed. Under the anesthesia, rats aged between 12-14 days after birth, were decapitated. The brain slices with 400 micron thickness including substantia nigra were obtained. After the treatment with enzyme, nigra neurons were acutely dissociated. The nystatin perforated patch recording were employed and the modulatory effects of monoamine on the GABA and taurine responses. The application of dopamine suppressed the GABA response. Taurine increased the membrane permeability to chloride ion by the activation of the glycine receptor-channel complex. Noradrenaline potentiated the taurine response, resulting in suppressing the neuronal excitability. The two distinct intracellular pathways were identified in the potentiation of the taurine responses by noradenaline. Activation of alpha2 adrenoceptor which is coupled to pertussis toxin-sensitive GTP binding protein suppresses adenyl cyclase activity, resulting in the decrease of intracellular cyclic AMP and protein kinase A activity. The decrease of protein kinase A activity potentiated the glycine receptor mediated taurine response.Another pathway in the modulation of taurine response by noradrenaline is as follows. Alpha2 adrenoceptor activated by noradrenaline increased the phospholipase C (PLC) activity through pertussis-toxin sensitive G protein. PLC increased the intracellular protein kinase C activity, resulting in the enhancement of glycine-receptor mediated taurine response. Single channel recording revealed that this enhancement of taurine response by alpha2 adrenoceptor activation was associated with the potentiation of the open probabillity of taurine-activated channel.These results indicate that noradrenaline enhanced the taurine response by the two distinct intracellular pathways in the rat substantia nigra neurons.