NO/cGMP/PKG 경로에 의한 캡사이신 채널의 활성 조절

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 inward currents (Icap) in dorsal root ganglion (DRG) neurons and the intracellular mechanism involved using the whole-cell patch clamp recording. The NO donor, sodium nitroprusside (SNP) reversibly decreased the amplitude of Icap in a dose-dependent manner. No significant inhibition was observed when SNP was applied together with the NO scavenger, hemoglobin (20 ？?). 8-Bromo-cGMP (100 ？?), a membrane permeable analog of cGMP, mimicked the effect of SNP. The effects of SNP on Icap were partially blocked by specific inhibitors of guanylyl cyclase, 1H-[1,2,4]oxidiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 ？?). Furthermore, non-specific inhibitor of phosphodiesterases, 3-isobutyl-1-methylxanthine (IBMX, 1 mM) augmented blocking effect of SNP. Pretreatment with the PKG inhibitor, KT 5823 (1 ？?) potentially abolished the effect of SNP on Icap. These results suggest that cGMP/PKG-dependent pathway may be involved in the NO-induced inhibition of Icap in rat DRG neurons.