title: Role of putrescine on androgen-elicited positive inotropism in the left atrium of rats.
abstract: Functional and biochemical studies were performed in isolated left atria of male Wistar rats to study whether endogenous polyamines may mediate androgen-elicited positive inotropism and their relationship with a rise in cAMP during the cardiotonic effect. 5 alpha-Dihydrotestosterone (100 microM) exposure increased intracellular putrescine as determined by HPLC, but it did not increase spermidine and spermine. This effect was antagonized by an inhibitor of ornithine decarboxylase, alpha-difluoromethylornithine (10 mM), suggesting enzyme activation. alpha-Difluoromethylornithine also antagonized androgens-elicited inotropism and the increase in intracellular cAMP. Putrescine (1 to 10 mM) elicited a concentration-dependent positive inotropism associated with the cAMP increase. The prior incubation with putrescine antagonized 5 alpha-dihydrotestosterone-elicited inotropism and did not produce sinergism on intracellular cAMP. Short-term incubation with 5 alpha-dihydrotestosterone or forskolin shifted to the left the cardiotonic effect of isoproterenol, an agonist of beta-adrenoceptors, without any increase in Emax, suggesting that a common mechanism was involved. Therefore, polyamines might modulate the cAMP production associated with the cardiotonic effect of androgens.
authors.affiliation: Farmacología, Departamento de Medicina, Universidad de Oviedo, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Velasco
authors.forename: Lorena
authors.initials: L
authors.lastname: Secades
authors.forename: Carmen
authors.initials: C
authors.lastname: Bordallo
authors.forename: Javier
authors.initials: J
authors.lastname: Bordallo
authors.forename: María José García
authors.initials: MJ
authors.lastname: de Boto
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Rubín
authors.forename: Agustín
authors.initials: A
authors.lastname: Hidalgo
authors.forename: Begoña
authors.initials: B
authors.lastname: Cantabrana
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D016275:Atrial Function / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology*; D000518:Eflornithine / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects / Q000201:enzymology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D065108:Ornithine Decarboxylase Inhibitors; D011700:Putrescine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D000728:Androgens; D002316:Cardiotonic Agents; D065108:Ornithine Decarboxylase Inhibitors; D013196:Dihydrotestosterone; D005576:Colforsin; D013096:Spermine; D000242:Cyclic AMP; D007545:Isoproterenol; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine