PMID: 15220780Jun 29, 2004Paper

Anesthetics inhibit acetylcholine-promoted guanine nucleotide exchange of heterotrimeric G proteins of airway smooth muscle

Anesthesiology
Chie SakiharaK A Jones

Abstract

Anesthetics inhibit airway smooth muscle contraction in part by a direct effect on the smooth muscle cell. This study tested the hypothesis that the anesthetics halothane and hexanol, which both relax airway smooth muscle in vitro, inhibit acetylcholine-promoted nucleotide exchange at the alpha subunit of the Gq/11 heterotrimeric G protein (Galphaq/11; i.e., they inhibit muscarinic receptor-Galphaq/11 coupling). The effect of halothane (0.38 +/- 0.02 mm) and hexanol (10 mm) on basal and acetylcholine-stimulated Galphaq/11 guanosine nucleotide exchange was determined in membranes prepared from porcine tracheal smooth muscle. The nonhydrolyzable, radioactive form of guanosine-5'-triphosphate, [S]GTPgammaS, was used as the reporter for Galphaq/11 subunit dissociation from the membrane to soluble fraction, which was immunoprecipitated with rabbit polyclonal anti-Galphaq/11 antiserum. Acetylcholine caused a significant time- and concentration-dependent increase in the magnitude of Galphaq/11 nucleotide exchange compared with basal values (i.e., without acetylcholine), reaching a maximal difference at 100 microm (35.9 +/-2.9 vs. 9.8 +/-1.2 fmol/mg protein, respectively). Whereas neither anesthetic had an effect on basal Galphaq/11 nu...Continue Reading

References

Dec 1, 1994·Journal of Pharmacological and Toxicological Methods·N Ali, D K Agrawal
Jan 1, 1994·Methods in Enzymology·J R HeplerA G Gilman
Sep 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·C A DoupnikP Kofuji
Feb 12, 1998·Neuron·W HeT G Wensel
Sep 9, 1998·The American Journal of Physiology·R W FreelN D Vaziri
Jan 31, 2002·Anesthesiology·Chie SakiharaDavid O Warner
Apr 19, 2002·Molecular Pharmacology·Yumiko IshizawaRoderic G Eckenhoff

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Citations

Apr 27, 2007·Journal of Anesthesia·Yumiko Ishizawa
Dec 21, 2007·Proceedings of the American Thoracic Society·Raymond B Penn, Jeffrey L Benovic

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