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Evidence for the participation of calcium in non‐genomic relaxations induced by androgenic steroids in rat vas deferens
Author(s) -
Lafayette S S L,
Vladimirova I,
GarcezdoCarmo L,
Monteforte P T,
Caricati Neto A,
Jurkiewicz A
Publication year - 2008
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/bjp.2008.18
Subject(s) - vas deferens , dihydrotestosterone , endocrinology , medicine , chemistry , iberiotoxin , androsterone , testosterone (patch) , androgen , flutamide , nitric oxide , potassium channel , androgen receptor , biology , hormone , steroid , prostate cancer , cancer
Background and purpose: Androgens cause non‐genomic relaxation in several smooth muscle preparations. However, such an effect has not been investigated in rat vas deferens yet. Our purpose was to study the effect of testosterone and derivatives in this tissue. Experimental approach: The influence of androgens was tested on contraction and translocation of intracellular Ca 2+ induced by KCl in rat vas deferens in vitro . Key results: The testosterone derivative 5α‐dihydrotestosterone produced a rapid and reversible concentration‐dependent relaxation of KCl‐induced contractions. Other androgens were also effective, showing the following rank order of potency: androsterone >5β‐dihydrotestosterone >androstenedione >5α‐dihydrotestosterone >testosterone. Calcium‐induced contractions were also inhibited (about 45%) by 5α‐dihydrotestosterone (30 μ M ). Moreover 5α‐dihydrotestosterone blocked the increase of intracellular Ca 2+ induced by KCl, measured by the fluorescent dye fura‐2. Relaxation to 5α‐dihydrotestosterone was resistant to the K + channel antagonists glibenclamide, 4‐aminopyridine and charybdotoxin. It was not affected by removal of epithelium or by L ‐NNA (300 μ M ), an inhibitor of nitric oxide biosynthesis, nor by selective inhibitors of soluble guanylate cyclase, ODQ or LY 83583, indicating that nitrergic or cGMP mediated mechanisms were not involved. The androgen‐induced relaxation was also not blocked by the protein synthesis inhibitor cycloheximide (300 μ M ) or by the classical androgen receptor flutamide (up to 100 μ M ), corroborating that the effect is non‐genomic. Conclusions and implications: Testosterone derivatives caused relaxation of the rat vas deferens, that did not involve epithelial tissue, K + channels, or nitric oxide‐dependent mechanisms, but was related to a partial blockade of Ca 2+ influx. British Journal of Pharmacology (2008) 153 , 1242–1250; doi: 10.1038/bjp.2008.18 ; published online 11 February 2008