AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 2 166-L172, Copyright © 1995 by American Physiological Society
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 and D. O. Warner
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota 55905.
Halothane relaxes airway smooth muscle in part by a direct effect on the
smooth muscle cell. The purpose of this 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 Ca(2+)-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 microM) 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.
