5-Hydroxytryptamine-Facilitated Release of Substance P from Rat Spinal Cord Slices Is Mediated by Nitric Oxide and Cyclic GMP |
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Authors: | Atsuko Inoue Takashi Hashimoto Izumi Hide Hiroaki Nishio Yoshihiro Nakata |
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Institution: | Department of Pharmacology, Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Hiroshima, Japan |
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Abstract: | 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 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-HT3 receptor antagonists), by N G-monomethyl- l -arginine (NMMA, a NO synthase inhibitor), and by methylene blue or 1 H -1,2,4]oxadiazolo4,3- 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. |
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Keywords: | Nitric oxide 5-Hydroxytryptamine 5-Hydroxytryptamine3 receptor Substance P release Spinal cord slice Cyclic GMP |
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