Inhibitory effects of halothane on the thermogenic pathway in brown adipocytes: localization to adenylyl cyclase and mitochondrial fatty acid oxidation

Biochemical Pharmacology
K B OhlsonJan Nedergaard

Abstract

Volatile anesthetics such as halothane efficiently inhibit nonshivering thermogenesis as well as the cellular manifestation of that phenomenon: norepinephrine-induced respiration in brown adipocytes. To identify the molecular site(s) of action of such anesthetics, we have examined the effect of halothane on the sequential intracellular steps from the interaction of norepinephrine with isolated brown adipocytes to the stimulation of mitochondrial respiration (=thermogenesis). We did not identify an inhibition at the level of the adrenergic receptors, but a first site of inhibition was identified as the generation of cAMP by adenylyl cyclase; this led to inhibition of norepinephrine-induced expression of the uncoupling protein-1 (UCP1) gene and reduced norepinephrine-induced lipolysis as secondary effects. Although an inhibition of lipolysis in itself would inhibit thermogenesis, circumvention of this inhibition revealed that a second, postlipolytic, site of inhibition existed: halothane also inhibited the stimulatory effect of exogenous fatty acids on cellular respiration. This inhibition was independent of the presence of UCP1 in the mitochondria of the cells and was thus not directly on the thermogenic uncoupling mechanism. Si...Continue Reading

References

Feb 1, 1979·Proceedings of the Society for Experimental Biology and Medicine·Y GangatL Triner
Mar 1, 1979·European Journal of Biochemistry·B Cannon, J Nedergaard
Jan 1, 1979·Methods in Enzymology·B Cannon, O Lindberg
Jun 1, 1978·Journal of Neurochemistry·S C Cheng, E A Brunner
Jan 1, 1975·Anesthesiology·R A Theye, J D Michenfelder
Nov 15, 1986·Biochemical Pharmacology·A ToninelloG Giron
Aug 1, 1973·Anesthesiology·P J Cohen
Feb 1, 1971·Archives of Biochemistry and Biophysics·R A HarrisP Jenkins
Apr 5, 1982·Life Sciences·K K McMahon, R J Schimmel
Jan 1, 1982·International Review of Cytology·J Nedergaard, O Lindberg
Jan 1, 1981·Pharmacology·G A Vergara, A Livingston
Aug 1, 1994·Journal of Pediatric Surgery·C T AlbaneseM I Rowe
Dec 23, 1999·The Journal of Biological Chemistry·G E BronnikovJ Nedergaard
Apr 20, 2000·The Journal of Biological Chemistry·J M LindquistJ Nedergaard
Apr 19, 2002·Molecular Pharmacology·Yumiko IshizawaRoderic G Eckenhoff
Jan 29, 2003·Anesthesiology·Kerstin B E OhlsonJan Nedergaard

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Citations

Jul 30, 2010·Journal of Perinatology : Official Journal of the California Perinatal Association·H Mendez-FigueroaM S Shinawi
Oct 12, 2010·Regulatory Toxicology and Pharmacology : RTP·Christine M HuntMark W Russo
Nov 26, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Christine M Hunt
May 21, 2008·Biochimica Et Biophysica Acta·Irina G ShabalinaJan Nedergaard
Mar 16, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Christine M HuntArie Regev
Dec 8, 2016·American Journal of Physiology. Endocrinology and Metabolism·Alexander W FischerNatasa Petrovic
Apr 4, 2013·Endocrine Reviews·Paul LeeKen K Y Ho
Apr 6, 2006·American Journal of Physiology. Endocrinology and Metabolism·Valeria GolozoubovaJan Nedergaard
May 3, 2007·American Journal of Physiology. Endocrinology and Metabolism·Jan NedergaardBarbara Cannon
Aug 8, 2021·International Journal of Molecular Sciences·Egor A TurovskyMaria V Turovskaya
Aug 18, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Tamires Duarte Afonso SerdanSandro Massao Hirabara

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