Racemic salbutamol administration to guinea-pigs selectively augments airway smooth muscle responsiveness to cholinoceptor agonists

Authors: Loss J.R.; Hock R.S.; Farmer S.G.¹; Orzechowski R.F.²

Source: Journal of Autonomic Pharmacology, Volume 21, Number 4, August 2001 , pp. 211-217(7)

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Abstract:

1 An aim of this study was to investigate whether continuous in vivo administration of a low dose of salbutamol to guinea-pigs alters the responsiveness of airway smooth muscle in vitro.

2 Osmotic minipumps containing a solution of racemic salbutamol were implanted subcutaneouly in guinea-pigs. The drug was infused at a dose of 0.2 mg kg^-1 day^-1 for 10 days and, at the end of that time, the trachea was isolated and concentration–response relationships to several contractile agonists were examined.

3 This treatment resulted in significant increases in the maximum tension developed by tracheal preparations in response to cholinoceptor agonists, carbachol and methacholine.

4 Cumulative concentration–response curves for histamine, leukotriene D4, and KCl were similar in tracheal segments from saline-control and salbutamol-infused animals.

5 Time course experiments showed that augmented airway contractile responsiveness to cholinoceptor agonists was reversible within 3 days after cessation of the 10 day salbutamol infusion.

6 Our findings support the hypothesis that bgr

₂-adrenoceptor agonist drugs, administered over time in vivo, induce a transient hyperresponsiveness of airway smooth muscle to cholinergic bronchoconstrictor stimuli.

Keywords: Copper ions; DNA binding dyes; Flourescent dyes; Pannergic PL; Receptors

Document Type: Research article

DOI: http://dx.doi.org/10.1046/j.1365-2680.2001.00229.x

Affiliations: 1: AstraZeneca R&D Lund, S-221 87 Lund, Sweden 2: Department of Pharmaceutical Sciences, University of the Sciences in Philadelphia, 600 South Forty-third Street, Philadelphia, PA 19104-4495, USA,

Publication date: 2001-08-01