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Non‐genomic effect of testosterone on airway smooth muscle
Author(s) -
Kouloumenta V,
Hatziefthimiou A,
Paraskeva E,
Gourgoulianis K,
Molyvdas P A
Publication year - 2006
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706936
Subject(s) - carbachol , endocrinology , testosterone (patch) , medicine , acetylcholine , flutamide , chemistry , nitric oxide , androgen , sodium nitroprusside , muscle relaxation , androgen receptor , receptor , hormone , prostate cancer , cancer
Background and purpose: Recent studies on blood vessels have provided evidence that testosterone may exert direct effects on smooth muscle. However, an acute effect on airway reactivity has not been shown yet. The aim of this study was to assess the direct effect of testosterone on the responsiveness of male adult rabbit airway smooth muscle (ASM), precontracted with 10 μM acetylcholine, 10μM carbachol or 80 mM KCl. Experimental approach: Contractility studies of rabbit tracheal smooth muscle were performed. Key results: Testosterone at concentrations of or above 1 nM had a significant relaxant effect on ASM precontracted with acetylcholine or carbachol, but did not affect ASM precontracted with KCl. The mechanical removal of airway epithelium as well as the inhibition of NO synthetase (by 100μM L‐NAME) reduced the relaxation caused by testosterone. The effect of testosterone was not altered by impairing prostanoid synthesis (by 10μM indomethacin). The nitric oxide donor, sodium nitroprusside, had the same relaxant effect on ASM precontracted with either carbachol or KCl. Inhibitors of androgen receptors (10μM flutamide) or DNA transcription (100μM actinomycin D) did not alter the effect of testosterone. Prolonged incubation of ASM with 100 nM or 100 μM testosterone for 24 or 48 h did not alter their responsiveness to acetylcholine. BSA‐testosterone (1pM to 100nM) relaxed significantly ASM precontracted with carbachol. The mechanical removal of airway epithelium abolished the relaxant effect of BSA‐testosterone. Conclusions and implications: Testosterone relaxes precontracted ASM via an epithelium and NO‐mediated way. This effect is mediated via a non‐genomic pathway. British Journal of Pharmacology (2006) 149 , 1083–1091. doi: 10.1038/sj.bjp.0706936