Phospholipase A2 activation enhances inhibitory synaptic transmission in rat substantia gelatinosa neurons

Phospholipase A(2) (PLA(2)) activation enhances glutamatergic excitatory synaptic transmission in substantia gelatinosa ( SG) neurons, which play a pivotal role in regulating nociceptive transmission in the spinal cord. By using melittin as a tool to activate PLA(2), we examined the effect of PLA(2) activation on spontaneous inhibitory postsynaptic currents ( sIPSCs) recorded at 0 mV in SG neurons of adult rat spinal cord slices by use of the whole cell patch-clamp technique. Melittin enhanced the frequency and amplitude of GABAergic and glycinergic sIPSCs. The enhancement of GABAergic but not glycinergic transmission was largely depressed by Na+ channel blocker tetrodotoxin or glutamate-receptor antagonists ( 6-cyano-7-nitroquinoxaline-2,3-dione and/ or DL-2-amino-5-phosphonovaleric acid) and also in a Ca2+-free Krebs solution. The effects of melittin on glycinergic sIPSC frequency and amplitude were dose-dependent with an effective concentration of similar to 0.7 mu M for half-maximal effect and were depressed by PLA(2) inhibitor 4-bromophenacyl bromide or aristolochic acid. The melittin-induced enhancement of glycinergic transmission was depressed by lipoxygenase inhibitor nordihydroguaiaretic acid but not cyclooxygenase inhibitor indomethacin. These results indicate that the activation of PLA(2) in the SG enhances GABAergic and glycinergic inhibitory transmission in SG neurons. The former action is mediated by glutamate-receptor activation and neuronal activity increase, possibly the facilitatory effect of PLA(2) activation on excitatory transmission, whereas the latter action is due to PLA(2) and subsequent lipoxygenase activation and is independent of extracellular Ca2+. It is suggested that PLA(2) activation in the SG could enhance not only excitatory but also inhibitory transmission, resulting in the modulation of nociception.