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5‐Hydroxytryptamine‐Facilitated Release of Substance P from Rat Spinal Cord Slices Is Mediated by Nitric Oxide and Cyclic GMP
Author(s) -
Inoue Atsuko,
Hashimoto Takashi,
Hide Izumi,
Nishio Hiroaki,
Nakata Yoshihiro
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.68010128.x
Subject(s) - substance p , soluble guanylyl cyclase , nitric oxide , chemistry , agonist , spinal cord , medicine , endocrinology , nitric oxide synthase , receptor , serotonin , pharmacology , neuropeptide , cyclic gmp , biochemistry , biology , neuroscience , organic chemistry
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 m M 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‐HT 3 receptor antagonists), by N G ‐monomethyl‐ l ‐arginine (NMMA, a NO synthase inhibitor), and by methylene blue or 1 H ‐[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‐HT 3 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‐HT 3 receptor and that the intracellular signaling is mediated via NO by an increase in cyclic GMP production.