Intracellular cAMP increases during the positive inotropism induced by androgens in isolated left atrium of rat.
Molecular interactions of androgens with the plasma membrane may produce rapid cardiovascular effects that cannot be explained by the classic genomic mechanisms. In this sense, 5 alpha- and 5 beta-dihydrotestosterone-induced an acute positive inotropic effect in isolated left atrium of rat, an effect which may be due to cAMP-dependent mechanisms. To prove this, intracellular levels of cAMP, after exposure to androgens in the organ bath, and binding to beta(1)-adrenoceptors were evaluated. After a 4-min exposure, 5 alpha- and 5 beta-dihydrotestosterone increased cAMP levels from 3.83+/-0.61 to 6.15+/-1.1 and 11.18+/-2.4 pmol cAMP/mg of protein, respectively. These increases were inhibited by atenolol and not modified by treatment of the rats with reserpine. The androgen-induced cAMP increase seems to be produced via an extracellular interaction, because positive inotropism and raised levels of cAMP were produced by 5 alpha-dihydrotestosterone conjugated with bovine serum albumin (BSA). In addition, it is independent of beta(1)-adrenoceptor activation, because neither androgen displaced [(3)H]dihydroalprenolol binding. Therefore, the androgens induced a positive inotropic effect via a postsynaptic effect that increases intracellular levels of cAMP. This effect is modulated by transcriptional mechanisms or by a protein with a short half-life.
Velasco
Lucía
L
Laboratorio de Farmacología, Departamento de Medicina, Facultad de Medicina, Universidad de Oviedo, Julián Clavería 6, Oviedo 33006, Spain.
Sánchez
Manuel
M
Rubín
José Manuel
JM
Hidalgo
Agustín
A
Bordallo
Carmen
C
Cantabrana
Begoña
B
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D016275:Atrial Function; D001667:Binding, Competitive / Q000187:drug effects; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism*; D004082:Dihydroalprenolol / Q000378:metabolism; D013196:Dihydrotestosterone / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000494:pharmacology; D014316:Tritium
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000728:Androgens; D010726:Phosphodiesterase Inhibitors; D013196:Dihydrotestosterone; D014316:Tritium; D012710:Serum Albumin, Bovine; D001262:Atenolol; D004082:Dihydroalprenolol; D012110:Reserpine; D000242:Cyclic AMP; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine