MODULATION OF CAPSAICIN-ACTIVATED CURRENTS BY NITRIC OXIDE IN CULTURED DORSAL ROOT GANGLION NEURONS IN RAT

초록

Nitric oxide (NO) modulates a variety of physiological functions, such as vasodilation, platelet aggregation, apoptosis and neurotransmission. The actions of NO primarily involve the activation of soluble guanylyl cyclase (sGC) that stimulates the production of cGMP as well as S-nitrosylation of proteins. In the present study, we investigated the effect of NO on capsaicin-activated channel in DRG neurons. The NO donor, sodium nitroprusside (SNP) at 1 - 1000 M blocked capsaicin-activated inward current (Icap) in dose-dependent manner. A sulfhydryl alkylating agent, N-ethylmaleimide (NEM, 2 mM) also blocked Icap. The blocking effect of SNP (100 M) on Icap was increased by subsequent addition of NEM (2 mM). Similarly, the blocking effect of NEM (2 mM) was also increased when SNP (100 M) in addition to NEM (2 mM) was applied. 8-Br-cGMP (100 M), a membrane-permeable form of cGMP, mimicked the effect of SNP. These results may have important implications for the inhibitory effect of NO on Icap in DRG neurons through both S-nitrosylation and NO-cGMP pathways.