Brain mitochondrial nitric oxide synthase: in vitro and in vivo inhibition by chlorpromazine

Archives of Biochemistry and Biophysics
S Lores-ArnaizA Boveris

Abstract

Mouse brain mitochondria have a nitric oxide synthase (mtNOS) of 147 kDa that reacts with anti-nNOS antibodies and that shows an enzymatic activity of 0.31-0.48 nmol NO/min mg protein. Addition of chlorpromazine to brain submitochondrial membranes inhibited mtNOS activity (IC50 = 2.0 +/- 0.1 microM). Brain mitochondria isolated from chlorpromazine-treated mice (10 mg/kg, i.p.) show a marked (48%) inhibition of mtNOS activity and a markedly increased state 3 respiration (40 and 29% with malate-glutamate and succinate as substrates, respectively). Respiration of mitochondria isolated from control mice was 16% decreased by arginine and 56% increased by NNA (Nomega-nitro-L-arginine) indicating a regulatory activity of mtNOS and NO on mitochondrial respiration. Similarly, mitochondrial H2O2 production was 55% decreased by NNA. The effect of NNA on mitochondrial respiration and H2O2 production was significantly lower in chlorpromazine-added mitochondria and absent in mitochondria isolated from chlorpromazine-treated mice. Results indicate that chlorpromazine inhibits brain mtNOS activity in vitro and can exert the same action in vivo.

References

Oct 1, 1989·The Biochemical Journal·A M AdamoA Boveris
Aug 1, 1983·Canadian Journal of Biochemistry and Cell Biology = Revue Canadienne De Biochimie Et Biologie Cellulaire·B D RoufogalisA Al-Jobore
Oct 20, 1995·Archives of Biochemistry and Biophysics·Y TakeharaK Utsumi
Jul 1, 1995·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·M FratelliP Ghezzi
Jan 5, 1996·Biochemical and Biophysical Research Communications·T E BatesJ B Clark
Jan 15, 1998·FEBS Letters·P Ghafourifar, C Richter
Jun 6, 1998·The Journal of Biological Chemistry·C GiuliviA Boveris
Jun 6, 1998·The Journal of Biological Chemistry·A Tatoyan, C Giulivi
Apr 25, 2000·Archives of Biochemistry and Biophysics·J BustamanteA Boveris
Jun 23, 2000·Annals of the New York Academy of Sciences·A BoverisE Cadenas
Dec 7, 2000·The Journal of Biological Chemistry·T M SarkelaC Giulivi
Feb 13, 2001·Trends in Biochemical Sciences·M Brunori
May 18, 2001·American Journal of Physiology. Heart and Circulatory Physiology·S FrenchR S Balaban
Nov 16, 2001·American Journal of Physiology. Heart and Circulatory Physiology·M C CarrerasJ J Poderoso
Nov 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·A J KanaiJ Peterson
May 8, 2002·Nature Reviews. Molecular Cell Biology·Salvador Moncada, Jorge D Erusalimsky
May 16, 2002·Nitric Oxide : Biology and Chemistry·Juanita BustamanteAlberto Boveris
Aug 3, 2002·The Journal of Biological Chemistry·Sarah Liv ElferingCecilia Giulivi
Aug 31, 2002·The Journal of Biological Chemistry·Natalia A RioboJuan J Poderoso
Oct 26, 2002·Free Radical Biology & Medicine·Alberto BoverisAna Navarro
Dec 17, 2002·Methods in Enzymology·Alberto BoverisAna Navarro
Feb 8, 2003·Science·Guy C Brown
May 24, 2003·Biochemical and Biophysical Research Communications·Silvia AlvarezAlberto Boveris
Jul 26, 2003·Antioxidants & Redox Signaling·Alberto BoverisAna Navarro
Nov 1, 2003·Antioxidants & Redox Signaling·Alberto BoverisLidia E Costa
Aug 27, 2005·Mitochondrion·Paul S Brookes

❮ Previous
Next ❯

Citations

Apr 6, 2005·Trends in Pharmacological Sciences·Pedram Ghafourifar, Enrique Cadenas
Sep 29, 2011·Dalton Transactions : an International Journal of Inorganic Chemistry·Somdatta Ghosh Dey, Abhishek Dey
Nov 18, 2004·Proceedings of the National Academy of Sciences of the United States of America·Fernando AntunesEnrique Cadenas
Jan 29, 2016·Neurochemical Research·Silvia Lores-ArnaizJuanita Bustamante
Jan 2, 2010·Free Radical Biology & Medicine·Hagir B SulimanClaude A Piantadosi
Aug 21, 2007·Biochimica Et Biophysica Acta·Analía CzerniczyniecSilvia Lores-Arnaiz
Nov 18, 2005·Neurochemistry International·Analía CzerniczyniecSilvia Lores-Arnaiz
Jul 12, 2005·Neurochemistry International·Silvia Lores-ArnaizAbraham Lemberg
Nov 7, 2006·Neuroscience·A CzerniczyniecS Lores-Arnaiz
Jul 31, 2012·Toxicology Letters·Jana Hroudová, Zdeněk Fišar
Nov 27, 2007·Biochemical and Biophysical Research Communications·Mordhwaj S PariharPedram Ghafourifar
Apr 21, 2006·Biochimica Et Biophysica Acta·Laura B ValdezAlberto Boveris
Apr 18, 2006·Biochimica Et Biophysica Acta·Alberto BoverisJuanita Bustamante
Oct 23, 2008·Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes·Ting LiYi Luo
Feb 8, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Gustavo F GonzalesAlberto Boveris
Jan 11, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Siva S V P SakamuriPrasad V G Katakam
May 8, 2021·Nitric Oxide : Biology and Chemistry·Analía G KaradayianSilvia Lores-Arnaiz
Jun 18, 2021·Neurochemistry International·Silvia Lores-ArnaizGeorgina Rodríguez de Lores Arnaiz

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antipsychotic Drugs

Antipsychotic drugs are a class of medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia and bipolar disorder. Discover the latest research on antipsychotic drugs here

© 2021 Meta ULC. All rights reserved