Halothane and pertussis toxin-sensitive G proteins in airway smooth muscle.
We hypothesized that halothane-induced depression of airway smooth muscle (AWSM) contractility is caused, in part, by an effect on pertussis toxin-sensitive guanosine triphosphate (GTP)-binding regulatory proteins (G proteins). To determine the effect of G protein inactivation on the ability of halothane to relax AWSM, isolated strips of canine tracheal smooth muscle were contracted with the muscarinic agonist acetylcholine and relaxed by halothane (0.2 to 1.6 minimum alveolar anesthetic concentration [MAC]). Half of the strips were treated with pertussis toxin 10 micrograms/mL. Because a pertussis toxin-sensitive G protein mediates muscarinic inhibition of adenylyl cyclase, depression of G protein function by halothane might also enhance the relaxing effects of beta-adrenoreceptor agonists. To test this possibility, in another series of experiments, the effect of pretreatment with 1.6 MAC halothane on the ability of isoproterenol to relax strips contracted with acetylcholine was studied; the converse order of drug presentation was also performed. Treatment with pertussis toxin did not affect the ability of halothane to relax AWSM; 1.6 MAC halothane produced a 42% +/- 8% (mean +/- SD) and 38% +/- 8% decrease in force in treated and untreated strips, respectively. Exposure to 1.6 MAC halothane did not significantly affect the dose-response relationship between isoproterenol and force. Conversely, exposure to isoproterenol (0.036 +/- 0.033 micron) did not significantly affect the dose-response relationship between halothane and force. These results do not support the presence of a significant effect of halothane on the function of pertussis toxin-sensitive G proteins.
Morimoto
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Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota 55905.
Yamamoto
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Jones
K A
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Warner
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DO
D000109:Acetylcholine / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000502:physiology; D000818:Animals; D003864:Depression, Chemical; D004285:Dogs; D004347:Drug Interactions; D004357:Drug Synergism; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology*; D037342:Pertussis Toxin; D011976:Receptors, Muscarinic / Q000502:physiology; D012680:Sensitivity and Specificity; D014132:Trachea / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D011976:Receptors, Muscarinic; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D000109:Acetylcholine; D006221:Halothane