Oxidation, Nitrosation, and Nitration of Serotonin by Nitric Oxide-Derived Nitrogen Oxides: Biological Implications in the Rat Vascular System

Autor: Jean-François Gallard, Maryvonne Dendane, Chantal Houée-Levin, Claire Ducrocq, Abdelhak Karim, Didier Payen, Jean-Marie Launay, Beatrice Blanchard
Rok vydání: 1997
Předmět:
Zdroj: Nitric Oxide. 1:442-452
ISSN: 1089-8603
DOI: 10.1006/niox.1997.0147
Popis: Because NO is not very reactive in an oxygen-free buffer, a significant part of serotonin (5-HT) is transformed by NO in nondeaerated phosphate buffer, at pH 7.4, into (4-serotonyl)-4-serotonin, 4-nitrososerotonin, and 4-nitroserotonin. Dimerization and above all nitrosation occur through the HNO2 reaction in the pH 4-6 range, possibly via radical mechanism involving N2O3. 5-HT is readily a substrate for nitrosation by HNO2 or N2O3, whereas tyrosine was described as not very reactive under the same conditions. Peroxynitrite converts 5-HT to the (4-serotonyl)-4-serotonin and to the 4-nitro derivative. In order to evaluate whether such structural modifications could modulate the biological properties of 5-HT, arterial pressure was measured after i.v. bolus injection of these derivatives to anesthetized rats. Injections of the 4-nitroso- and 4-nitro-5-HT resulted in first a brief hypotensive response and did not give the subsequent hypertensive and hypotensive phases observed with 5-HT. Finally, when tested on some cloned rat 5-HT receptors stably transfected into LMTK- cells, both 4-nitroso and 4-nitro derivatives behaved as agonists and antagonists toward 5-HT1B and 5-HT2B receptors, respectively.
Databáze: OpenAIRE