Nitric oxide modulates the release of serotonin in the rat hypothalamus.
To investigate the effect of nitric oxide (NO) on the release of serotonin and its main metabolite, 5-hydroxyindoleacetic acid (5-HIAA), the posterior hypothalamus of the conscious rat was superfused through a push-pull cannula with drugs which either liberate NO, or inhibit NO synthase (NOS). The NO donors, linsidomine, diethylamine/nitric oxide (DEA/NO), S-nitroso-N-acetylpenicillamine (SNAP), S-nitroso-glutathione (SNOG) and sodium nitroprusside influenced the release of serotonin in a biphasic way. Low concentrations of drugs diminished, while higher concentrations of these compounds enhanced the outflow of serotonin. The NOS inhibitors N(G)-methyl-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NINA) enhanced the serotonin release. A high concentration of L-NAME slightly diminished the outflow of serotonin. Inhibition of the guanylyl cyclase by oxodiazolo[4, 3]quinoxaline-one (ODQ) abolished the changes in serotonin outflow induced by both low and high concentrations of linsidomine. The extracellular concentration of the 5-HIAA was not influenced by the compounds used. These data suggest that endogenous NO modulates the release of serotonin in a biphasic and cGMP-dependent way.
Department of Pharmacology and Toxicology, University of Innsbruck, Peter-Mayr-Strasse 1, Innsbruck A-6020, Austria.
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Kaehler
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Singewald
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Sinner
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Philippu
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D007034:Hypothalamus, Posterior / Q000187:drug effects* / Q000378:metabolism; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026422:S-Nitrosoglutathione; D012701:Serotonin / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007191:Indazoles; D009603:Nitroso Compounds; C110881:S-nitro-N-acetylpenicillamine; D009599:Nitroprusside; D009569:Nitric Oxide; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D026422:S-Nitrosoglutathione; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D005978:Glutathione; D010396:Penicillamine; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester