title: Evidence for the participation of calcium in non-genomic relaxations induced by androgenic steroids in rat vas deferens.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  The influence of androgens was tested on contraction and translocation of intracellular Ca(2+) induced by KCl in rat vas deferens in vitro.
  
  
  RESULTS
  The testosterone derivative 5alpha-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 >5beta-dihydrotestosterone >androstenedione >5alpha-dihydrotestosterone >testosterone. Calcium-induced contractions were also inhibited (about 45%) by 5alpha-dihydrotestosterone (30 microM). Moreover 5alpha-dihydrotestosterone blocked the increase of intracellular Ca(2+) induced by KCl, measured by the fluorescent dye fura-2. Relaxation to 5alpha-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 microM), 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 microM) or by the classical androgen receptor flutamide (up to 100 microM), corroborating that the effect is non-genomic.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: S S L
authors.initials: SS
authors.lastname: Lafayette
authors.forename: I
authors.initials: I
authors.lastname: Vladimirova
authors.forename: L
authors.initials: L
authors.lastname: Garcez-do-Carmo
authors.forename: P T
authors.initials: PT
authors.lastname: Monteforte
authors.forename: A
authors.initials: A
authors.lastname: Caricati Neto
authors.forename: A
authors.initials: A
authors.lastname: Jurkiewicz
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000735:Androstenedione / Q000494:pharmacology; D000738:Androsterone / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000494:pharmacology*; D014649:Vas Deferens / Q000187:drug effects* / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000728:Androgens; D015221:Potassium Channels; D013196:Dihydrotestosterone; D009569:Nitric Oxide; D013739:Testosterone; D000735:Androstenedione; D011189:Potassium Chloride; D000738:Androsterone; D002118:Calcium