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Paradoxal effect of salbutamol in an in vitro model of bronchoprotection
Author(s) -
Girodet P.O.,
Berger P.,
Martinez B.,
Marthan R.,
Advenier C.,
Molimard M.
Publication year - 2005
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2005.00320.x
Subject(s) - salbutamol , acetylcholine , propranolol , antagonist , muscarinic antagonist , endocrinology , chemistry , medicine , pharmacology , calcium , atenolol , asthma , receptor , blood pressure
Salbutamol‐induced hyperresponsiveness to acetylcholine was investigated in human and guinea‐pig isolated airways and cultured human airway smooth muscle cells. Salbutamol (10 −7 –10 −5 m ) inhibited contractions induced by low concentrations of acetylcholine (10 −8 –10 −7 m ) but potentiated contractions induced by higher concentrations of acetylcholine (10 −5 –10 −3 m ). Pretreatment with the calcium channel antagonist nicardipine suppressed salbutamol‐induced hyperresponse. Stimulation of cultured human airway smooth muscle cells with salbutamol (10 −6 m ) amplified intracellular calcium concentration rise induced by acetylcholine (10 −5 m ). Propranolol (10 −7 m ), a β 1 ‐ and β 2 ‐adrenoceptor antagonist, and ICI 118551 (10 −7 –10 −6 m ), a β 2 ‐adrenoceptor antagonist, suppressed the inhibitory effect of salbutamol but did not inhibit the hyperresponse on high concentrations of acetylcholine. In contrast, higher concentration of propranolol (10 −6 m ) inhibited salbutamol‐induced hyperreactivity. Effects of salbutamol were not affected by atenolol, a β 1 ‐adrenoceptor blocker. Salbutamol‐induced hyperresponsiveness is mediated through a mechanism involving calcium channel activation.