5‐Hydroxytryptamine‐Facilitated Release of Substance P from Rat Spinal Cord Slices Is Mediated by Nitric Oxide and Cyclic GMP

Publisher Website
Google Scholar
Abstract
The role of nitric oxide (NO) in the control of 5‐hydroxytryptamine (5‐HT)‐induced release of substance P was investigated in rat spinal cord in vitro. 5‐HT facilitated the 60 mM K+‐evoked release of substance P‐like immunoreactive materials (SPLI) from the superfused rat dorsal spinal cord slices without affecting spontaneous SPLI release. The facilitatory effect of 5‐HT was significantly inhibited by ICS 205‐930 or granisetron (potent and specific 5‐HT3 receptor antagonists), by NG‐monomethyl‐l‐arginine (NMMA, a NO synthase inhibitor), and by methylene blue or 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxaline‐1‐one (MB or ODQ, respectively; both are inhibitors of soluble guanylyl cyclase) and was mimicked by 2‐methylserotonin (2‐m‐5‐HT, a selective 5‐HT3 receptor agonist), l‐arginine (a precursor of NO), or 8‐bromo‐cyclic GMP. NMMA, MB, or ODQ inhibited the 2‐m‐5‐HT‐induced increase of cyclic GMP levels in the rat dorsal spinal cord slices. These data suggest that the facilitatory effect of 5‐HT on the release of SPLI is mediated by the 5‐HT3 receptor and that the intracellular signaling is mediated via NO by an increase in cyclic GMP production.

This publication has 0 references indexed in Scilit: