title: Contractile effect of 6 beta-acetoxy nortropane on human and guinea pig airways.
abstract: OBJECTIVE
  To study the effects of 6 beta-acetoxy nortropane (6 beta-AN) on the isolated human bronchus and guinea pig trachea.
  
  
  METHODS
  The contractile effect of 6 beta-AN was studied with 4 different muscarinic receptor antagonists on airway strips and inositol phosphates (IP) accumulation in human bronchi was determined by HPLC with radioactivity flow detector.
  
  
  RESULTS
  (1) The maximal contractile effect of 6 beta-AN was lower than that of acetylcholine (ACh) on the human bronchus and equal to that of ACh on the guinea pig trachea. 6 beta-AN was more potent than ACh on both preparations (68 and 245 times, respectively). (2) The contractile effect of 6 beta-AN was inhibited by atropine (1 -100 nmol.L-1) or para-fluoro-hexahydro-sila-difenidol (0.01-1 mumol.L-1), but not by methoctramine (Met, 0.3-3 mumol.L-1) or pirenzepine (0.01-0.1 mumol.L-1), and was not enhanced by tacrine (0.1-10 mumol.L-1) or by epithelium removal. (3) The 6 beta-AN induced-contraction was accompanied by an increase of IP levels in isolated human bronchial tissues. (4) 6 beta-AN had an inhibitory effect on isoprenaline (Iso)-induced relaxation, which was abolished or reduced by Met 0.3 mumol.L-1.
  
  
  CONCLUSIONS
  6 beta-AN exerts a potent contractile effect involving muscarinic M3 receptor stimulation on airway smooth muscle. Muscarinic M2 receptor stimulation is furthermore partially involved in the antagonism by 6 beta-AN on the Iso-induced relaxation of the guinea pig trachea.
authors.affiliation: Faculté de Médecine Paris-Ouest, France. yaoli@shsmu.edu.cn
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Moreau
authors.forename: M
authors.initials: M
authors.lastname: Molimard
authors.forename: E
authors.initials: E
authors.lastname: Naline
authors.forename: A
authors.initials: A
authors.lastname: Bisson
authors.forename: C
authors.initials: C
authors.lastname: Advenier
mesh_terms: D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D009662:Nortropanes / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects
chemical_list: D007295:Inositol Phosphates; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D009662:Nortropanes; C071344:6-acetoxynortropane