Evidence for the participation of calcium in non-genomic relaxations induced by androgenic steroids in rat vas deferens

• Autor(a) principal: Lafayette, Simone Sette Lopes [UNIFESP]
• Data de Publicação: 2008
• Outros Autores: Vladimirova, Irina [UNIFESP], Garcez-do-Carmo, Lucia [UNIFESP], Monteforte, Priscila Totarelli [UNIFESP], Caricati-Neto, Afonso [UNIFESP], Jurkiewicz, Aron [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://repositorio.unifesp.br/handle/11600/30452; http://dx.doi.org/10.1038/bjp.2008.18
• topic: androgen; dihydrotestosterone; non-genomic action; rat vas deferens; calcium

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 Ca2+ induced by KCl in rat vas deferens in vitro.Key results: the testosterone derivative 5 alpha-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 >5 beta-dihydrotestosterone >androstenedione >5 alpha-dihydrotestosterone >testosterone. Calcium-induced contractions were also inhibited (about 45%) by 5 alpha-dihydrotestosterone (30 mu M). Moreover 5 alpha-dihydrotestosterone blocked the increase of intracellular Ca2+ induced by KCl, measured by the fluorescent dye fura-2. Relaxation to 5 alpha-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 mM), 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 mu M) or by the classical androgen receptor flutamide (up to 100 mu 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 Ca2+ influx.