[Recent advances in molecular pharmacology of cellular signalling mechanism].
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 -60mV) 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/G0, 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 cAMP-dependent 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.
Nomura
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Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002713:Chlorine / Q000378:metabolism; D005071:Evoked Potentials / Q000187:drug effects; D007473:Ion Channels / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D009865:Oocytes / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D012333:RNA, Messenger; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D014981:Xenopus
C029152:G-substrate; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D010716:Phosphatidylinositols; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D012701:Serotonin; D002713:Chlorine; D011494:Protein Kinases; D002118:Calcium