title: Droperidol inhibits tracheal contraction induced by serotonin, histamine or carbachol in guinea pigs.
abstract: OBJECTIVE
  Droperidol (D) is effective in the treatment of patients with status asthmaticus. It has been reported that D inhibits the bronchoconstriction induced by serotonin (5-HT) but not that by histamine (H) or acetylcholine. However, haloperidol, another butyrophenone, is known to interact with and inhibit calmodulin, an intracellular Ca(++)-binding protein which is important in the contraction of smooth muscles. The present study was designed to investigate the effects of D on tracheal contractions induced by 5-HT, H or carbachol (C) and to determine the contribution of alpha-adrenoceptors to the relaxant effect of D in vitro.
  
  
  METHODS
  Tracheas of female guinea pigs were cut spirally into strips and mounted in water-jacketed organ baths in Tyrode's solution, aerated with a mixture of 95% O2 and 5% CO2 at 37 degrees C. The changes in isometric tension induced by each spasmogen in the strips were measured with a transducer and a polygraph.
  
  
  RESULTS
  We found that D inhibited the tracheal contractions induced by 5-HT, H or C in a concentration-dependent manner. At 1.25 x 10(-6) M D blocked the effect of 10(-4) M 5-HT by 44.1 +/- 4.3% and at 2.5 x 10(-6) M by 63.8 +/- 3.8%. Similarly, at 5.0 x 10(-6) M concentration, D blocked the effect of 10(-5) M H by 27.7 +/- 5.3% and at 10(-5) M by 56.2 +/- 2.6%. Furthermore, 5 x 10(-6) M of D reduced the contractions produced by 10(-7) M C by 37.1 +/- 3.0% and 10(-5) M of D by 76.1 +/- 3.2%. The inhibiting effect of D was strongest on contractions induced by 5-HT. Prazosin (10(-6) M) affected neither 5-HT-induced contractions nor the inhibition by D.
  
  
  CONCLUSIONS
  Our data indicate that D partially blocks the contractile responses not only to 5-HT, an effect which would be mediated through a blockade of the 5-HT receptors, but also to H or C, probably through inhibition of calmodulin. Our data support previous reports indicating that droperidol may be an important therapeutic agent in the treatment of patients with hyperreactive airways.
authors.affiliation: Department of Anesthesiology, University of Illinois College of Medicine at Chicago, USA.
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.forename: K
authors.initials: K
authors.lastname: Hirota
authors.forename: A
authors.initials: A
authors.lastname: Matsuki
authors.forename: E K
authors.initials: EK
authors.lastname: Zsigmond
authors.forename: S F
authors.initials: SF
authors.lastname: Rabito
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D004329:Droperidol / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
chemical_list: D018686:Anesthetics, Intravenous; D018721:Muscarinic Agonists; D012701:Serotonin; D006632:Histamine; D002217:Carbachol; D004329:Droperidol; D011224:Prazosin