細胞の薬物応答系とその機構をめぐって

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Important findings on the molecular and regulatory properties of neurotransmitter receptors, GTP-proteins, ion channels and protein kinases were briefly reviewed. On the basis of recent advances in the theme mentioned above, we investigated the transmembrane signalling mechanism of serotonin (5-HT)-evoked inward current responses under the voltage clamp condition (holding at -60 mV) in Xenopus oocytes injected with rat brain poly(A)+ mRNA, suggesting that 5-HT evokes a Cl- current via such a mechanism as follows: 1) activation of 5-HT1C subtype of receptors, 2) activation of pertussis toxin-sensitive Gi; Go, 3) phospholipase C activation, 4) inositol 1, 4, 5-trisphosphate (IP3) formation, 5) an increase of [Ca2+]i liberated by IP3, and 6) gating of Cl channels stimulated perhaps by Ca2+-calmodulin. On the other hand, protein kinase C (C-kinase) activation by diacylglycerol and Ca2+ seems to cause a feedback inhibition to the 5-HT responses by phosphorylation of certain proteins. Voltage-operated Ca channels of the N-type reconstituted in oocytes injected with brain mRNA seem to be modulated by C-kinase as well as by cAMPdependent protein kinase. Significances of oocytes using as a model system to analyze the molecular mechanism of neuronal signalling in the brain were stressed and reviewed.
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