Role of putrescine on androgen-elicited positive inotropism in the left atrium of rats.
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.
Velasco
Lucía
L
Farmacología, Departamento de Medicina, Universidad de Oviedo, Spain.
Secades
Lorena
L
Bordallo
Carmen
C
Bordallo
Javier
J
de Boto
María José García
MJ
Rubín
José Manuel
JM
Hidalgo
Agustín
A
Cantabrana
Begoña
B
Sánchez
Manuel
M
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
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