Contractile effect of 6 beta-acetoxy nortropane on human and guinea pig airways
Zhang, Y.; Moreau, J.; Molimard, M.; Naline, E.; Bisson, A.; Advenier, C.
Zhongguo Yao Li Xue Bao 19(3): 211-217
1998
ISSN/ISBN: 0253-9756 PMID: 10375728 Document Number: 487177
To study the effects of 6 beta-acetoxy nortropane (6 beta-AN) on the isolated human bronchus and guinea pig trachea. 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. (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. 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.