Anesthetics inhibit membrane receptor coupling to the Gq/11 heterotrimeric G protein in airway smooth muscle

Tetsuzo Nakayama, Masao Hayashi, David O. Warner, Keith A. Jones

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Background: Some anesthetics relax airway smooth muscle in part by inhibiting acetylcholine-induced increases in Ca2+ sensitivity, an effect associated with inhibition of guanosine nucleotide exchange at the α subunit of the Gq/11 (Gαq/11) heterotrimeric G protein. This study tested the hypothesis that these anesthetic effects are not unique to the muscarinic receptor but are a general property of the heptahelical receptors that increase Ca2+ sensitivity in airway smooth muscle. Methods: Anesthetic effects on agonist-induced increases in Ca2+ sensitivity were measured in porcine airway smooth muscle strips permeabilized with S. aureus α-toxin. Anesthetic effects on basal (without agonist stimulation) and agonist-promoted Gαq/11 guanosine nucleotide exchange were determined in crude membranes prepared from porcine airway smooth muscle. The nonhydrolyzable, radioactive form of guanosine 5′-triphosphate was used as the reporter for nucleotide exchange at Gαq/11. Results: Acetylcholine, endothelin-1, and histamine caused a concentration-dependent increase in Ca2+ sensitivity. Halothane (0.67 ± 0.07 HIM) and hexanol (10 mM) significantly inhibited the increase in Ca2+ sensitivity induced by each agonist. Each agonist also caused a time- and concentration-dependent increase in Gαq/11 nucleotide exchange. Neither anesthetic had an effect on basal Gαq/11 nucleotide exchange, whereas halothane and hexanol significantly inhibited the increase in Gαq/11 nucleotide exchange promoted by each agonist. Conclusion: These data suggest that inhibition of agonist-promoted guanosine nucleotide exchange at Gαq/11 by some anesthetics may be a general property of heptahelical receptors involved cellular processes mediated by Gαq/11, including muscarinic, endothelin-1, and histamine receptor activation of Ca2+ sensitivity.

Original languageEnglish (US)
Pages (from-to)296-305
Number of pages10
JournalAnesthesiology
Volume103
Issue number2
DOIs
StatePublished - Aug 2005

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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