Ethanol attenuates contraction of primary cultured rat airway smooth muscle cells.

American Journal of Respiratory Cell and Molecular Biology
Peter J OldenburgJ H Sisson

Abstract

Airway smooth muscle cells are the main effector cells involved in airway narrowing and have been used to study the signaling pathways involved in asthma-induced airway constriction. Our previous studies demonstrated that ethanol administration to mice attenuated methacholine-stimulated increases in airway responsiveness. Because ethanol administration attenuates airway responsiveness in mice, we hypothesized that ethanol directly blunts the ability of cultured airway smooth muscle cells to shorten. To test this hypothesis, we measured changes in the size of cultured rat airway smooth muscle (RASM) cells exposed to ethanol (100 mM) after treatment with methacholine. Ethanol markedly attenuated methacholine-stimulated cell shortening (methacholine-stimulated length change = 8.3 ± 1.2% for ethanol versus 43.9 ± 1.5% for control; P < 0.001). Ethanol-induced inhibition of methacholine-stimulated cell shortening was reversible 24 hours after removal of alcohol. To determine if ethanol acts through a cGMP-dependent pathway, incubation with ethanol for as little as 15 minutes produced a doubling of cGMP-dependent protein kinase (PKG) activity. Furthermore, treatment with the PKG antagonist analog Rp-8Br-cGMPS (10 μM) inhibited ethanol...Continue Reading

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Citations

Nov 25, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Peter J OldenburgJoseph H Sisson
Jan 2, 2016·Toxicology and Applied Pharmacology·Lata KaphaliaWilliam J Calhoun
Jul 15, 2015·European Journal of Pharmacology·Fatma AydinogluNuran Ogulener

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