5-Hydroxytryptamine-facilitated release of substance P from rat spinal cord slices is mediated by nitric oxide and cyclic GMP.
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.
Inoue
A
A
Department of Pharmacology, Hiroshima University School of Medicine, Japan.
Hashimoto
T
T
Hide
I
I
Nishio
H
H
Nakata
Y
Y
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000819:agonists; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*
D018040:Receptors, Neurokinin-1; D009569:Nitric Oxide; D012701:Serotonin; D013373:Substance P; C045918:2-methyl-5-HT; D006152:Cyclic GMP