TY - JOUR
T1 - Halothane reduces force and intracellular Ca2+ in airway smooth muscle independently of cyclic nucleotides
AU - Jones, K. A.
AU - Lorenz, R. R.
AU - Morimoto, N.
AU - Sieck, G. C.
AU - Warner, D. O.
PY - 1995
Y1 - 1995
N2 - 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).
AB - 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).
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U2 - 10.1152/ajplung.1995.268.2.l166
DO - 10.1152/ajplung.1995.268.2.l166
M3 - Article
C2 - 7532366
AN - SCOPUS:0028939004
SN - 1040-0605
VL - 268
SP - L166-L172
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 2 12-2
ER -