Halothane reduces force and intracellular Ca2+ in airway smooth muscle independently of cyclic nucleotides

K. A. Jones, R. R. Lorenz, N. Morimoto, G. C. Sieck, D. O. Warner

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Halothane relaxes airway smooth muscle in part by a direct effect on the smooth muscle cell. The purpose of tiffs study was to investigate the possible role of cyclic nucleotides in this direct effect. Strips of canine tracheal smooth muscle in vitro were contracted with acetylcholine (ACh) and then exposed to 0.7-2.6% halothane. Isometric force and the intracellular concentrations of adenosine cyclic 3',5'-monophosphate ([cAMP](i)), guanosine cyclic 3',5'-monophosphate ([cGMP](i)), and free calcium ([Ca2+](i), using the fluorescent Ca2+-sensitive dye fura 2) were measured. ACh caused significant increases in force, [cAMP](i), [cGMP](i), and [Ca2+](i). Subsequent exposure of the strips to halothane caused an additional increase in [cAMP](i), decreases in force and [Ca2+](i), and no effect on [cGMP](i). The additional increase in [cAMP](i) was similar to that produced by a concentration of isoproterenol (0.03 μM) that caused equipotent relaxation. Indomethacin abolished the increase in [cAMP](i) produced by ACh and abolished the additional increase in [cAMP](i) produced by halothane. In contrast, indomethacin had no effect on the decreases in force and [Ca2+](i). These findings suggest that in canine tracheal smooth muscle contracted with ACh 1) halothane increases [cAMP](i) by a cyclooxygenase- dependent mechanism and 2) the increase in [cAMP](i) produced by halothane is not responsible for the relaxation or the decrease in [Ca2+](i).

Original languageEnglish (US)
Pages (from-to)L166-L172
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume268
Issue number2 12-2
DOIs
StatePublished - 1995

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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