title: Effects of ketamine on neostigmine-induced contractile and phosphatidylinositol responses of the rat trachea.
abstract: OBJECTIVE
  Neostigmine causes airway smooth muscle contraction through the direct stimulation of muscarinic receptors and the activation of phosphatidylinositol (PI) responses. Ketamine attenuates airway smooth muscle contraction. It is not clear whether ketamine attenuates neostigmine-induced airway smooth muscle contraction by inhibiting the PI response. This study was designed to examine the effects of ketamine on neostigmine-induced contractile and PI responses of the rat trachea.
  
  
  METHODS
  Thirty male Wistar rats weighing 250-350 g were used. In the experiment on the contractile response, active contraction was induced with 1 microM neostigmine in the presence or absence of ketamine. In the experiment on the phosphatidylinositol response, the trachea slices were incubated with [3H]myo-inositol, 1 microM neostigmine, or 100 microM aluminum fluoride, and ketamine. The formation of [3H]inositol monophosphate (IP1), a degradation product of the phosphatidylinositol response, was measured with a liquid scintillation counter. Statistical significance (P < 0.05) was determined by analysis of variance.
  
  
  RESULTS
  Neostigmine 1 microM caused tracheal ring contraction. This contraction was attenuated by ketamine dose-dependently and reached resting tension at 100 microM. Neostigmine- and aluminum fluoride-induced IP1, accumulation was also attenuated by ketamine.
  
  
  CONCLUSIONS
  The results suggest that ketamine attenuates neostigmine-induced contractile responses, at least in part, through the inhibition of phospholipase C coupled with G protein in the PI response.
authors.affiliation: Department of Anesthesiology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Saito
authors.forename: Osamu
authors.initials: O
authors.lastname: Shibata
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Makita
authors.forename: Koji
authors.initials: K
authors.lastname: Sumikawa
mesh_terms: D017607:Aluminum Compounds / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005459:Fluorides / Q000494:pharmacology; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009388:Neostigmine / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000378:metabolism / Q000502:physiology*
chemical_list: D017607:Aluminum Compounds; D018686:Anesthetics, Intravenous; D002800:Cholinesterase Inhibitors; D010716:Phosphatidylinositols; D009388:Neostigmine; D007649:Ketamine; D005459:Fluorides; C032311:aluminum fluoride