<b>Phospholipase A<sub>2</sub> activation enhances inhibitory synaptic transmission in the rat substantia gelatinosa</b>

Abstract

The activation of phospholipase A2 (PLA2) is known to enhance glutamatergic transmission in substantia gelatinosa (SG; lamina II of Rexed) neurons that play a pivotal role in regulating nociceptive transmission to the spinal dorsal horn from the periphery. In order to know in detail a role of PLA2 in regulating nociceptive transmission, we examined the effect of a PLA2 activator melittin on inhibitory synaptic transmission by applying the blind whole-cell patch-clamp technique to SG neurons in spinal cord slices prepared from male adult rats. Melittin (1 µM) superfused for 3 min enhanced the amplitude and the frequency of GABAergic and glycinergic spontaneous inhibitory postsynaptic currents (sIPSCs). The enhancement of GABAergic sIPSC was largely depressed by a Na+-channel blocker tetrodotoxin (TTX; 0.5 µM), whereas that of glycinergic sIPSC was not affected by TTX. These effects of melittin were depressed in extent by a PLA2 inhibitor 4-bromophenacyl bromide (10 - 50 µM). Bee venom PLA2 (0.1 unit/ml) itself did not affect glycinergic sIPSCs. The effect of melittin on glycinergic sIPSCs was seen in the presence of a protein kinase C activator phorbol 12,13-dibutyrate (PDBu; 0.5 µM); this extent was not significantly different from that in the absence of PDBu. The enhancement of glycinergic sIPSC produced by melittin was unaffected by a cyclooxygenase inhibitor indomethacin (100 µM), while being not seen in the presence of a lipoxygenase inhibitor nordihydroguaiaretic acid (100 µM). Leukotriene B4 (0.1 - 0.5 µM) did not affect glycinergic sIPSCs. These results indicate that the activation of PLA2 in the SG enhances GABAergic and glycinergic transmission in SG neurons. The former action is mediated by the facilitatory effect of PLA2 activation on excitatory transmission, leading to an increase in the electrical activities of SG neurons, while the latter action is due to PLA2 and subsequent lipoxygenase activation where metabolites other than leukotriene B4 are probably involved in enhancing glycinergic transmission. It is suggested that PLA2 activation in the SG could enhance not only excitatory but also inhibitory transmission, resulting in the modulation of nociceptive transmission from the periphery.