The effects of 5-HT and NA on glycine-gated Cl- channel currents(IGly) and its intracellular mechanisms were investigated in acutely dissociated rat sacral dorsal commissural neurons by using nystatin perforated patch clamp recording. It was found that: (1) the activation of 5-HT2 receptor coupled to IAP-insensitive G-proteins increases intracellular DAG formation through the activation of phospholipase C(PLC). The accumulation of DAG increases the Ca(2+)-independent or novel PKC(nPKC) activity, resulting in the potentiation of IGly; (2) the activation of alpha 2-adrenoceptor by NA coupled to IAP-sensitive G-proteins reduces intracellular cAMP formation through the inhibition of adenylyl cyclase (AC). The reduction of cAMP decreases PKA activity, resulting in the potentiation of IGly.