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 (I-Gly) 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 I-Gly, thus indicating the 5-HT2 receptor-mediated enhancement. 4. Phorbol-12-myristate-13-acetate and 1-oleoyl-2-acetylglycerol potentiated I-Gly. The subsequent application of 5-HT slightly increased I-Gly. Chelerythrine blocked the enhancement of I-Gly by 5-HT, thus suggesting the involvement of protein kinase C (PKC) in the pathway of 5-HT action on I-Gly. 5. Pertussis toxin (IAP) treatment did not block the facilitatory effect of 5-HT on I-Gly. 6. BAPTA AM did not disturb the 5-HT-induced potentiation of I-Gly, 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 Ca2+-independent PKC activity, thus resulting in the potentiation of the Gly response in the SDCN neurones.