Protein kinase C-mediated enhancement of glycine response in rat sacral dorsal commissural neurones by serotonin.
1. The modulatory effect of serotonin (5-hydroxytryptamine, 5-HT), on the glycine (Gly) response was investigated in neurones acutely dissociated from the rat sacral dorsal commissural nucleus (SDCN) using a nystatin-perforated patch recording configuration. 2. 5-HT potentiated the 10(-5) M Gly-induced Cl- current (IGly) in a concentration-dependent manner without changing the reversal potential of the Gly response or the affinity of Gly to its receptor. 3. alpha-Methyl-5-HT mimicked and ketanserine blocked the 5-HT action on IGly, thus indicating the 5-HT2 receptor-mediated enhancement. 4. Phorbol-12-myristate-13-acetate and 1-oleoyl-2-acetylglycerol potentiated IGly. The subsequent application of 5-HT slightly increase IGly. Chelerythrine blocked the enhancement of IGly by 5-HT, thus suggesting the involvement of protein kinase C (PKC) in the pathway of 5-HT action on IGly. 5. Pertussis toxin (IAP) treatment did not block the facilitatory effect of 5-HT on IGly. 6. BAPTA AM did not disturb the 5-HT-induced potentiation of IGly, thus suggesting that [Ca2+]i is not involved in the 5-HT effect. 7. In conclusion, activation of a 5-HT2 receptor coupled to an IAP-insensitive G-protein increases intracellular diacylglycerol (DAG) formation. The accumulation of DAG also increases the Ca(2+)-independent PKC activity, thus resulting in the potentiation of the Gly response in the SDCN neurones.
Department of Physiology, Kyushu University Faculty of Medicine, Fukuoka, Japan.
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Xu
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Nabekura
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Akaike
D000818:Animals; D002118:Calcium / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000187:drug effects / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D002614:Chelating Agents; D018009:Receptors, Glycine; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D002118:Calcium