title: Intracellular cAMP increases during the positive inotropism induced by androgens in isolated left atrium of rat.
abstract: 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.
authors.affiliation: Laboratorio de Farmacología, Departamento de Medicina, Facultad de Medicina, Universidad de Oviedo, Julián Clavería 6, Oviedo 33006, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Velasco
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Rubín
authors.forename: Agustín
authors.initials: A
authors.lastname: Hidalgo
authors.forename: Carmen
authors.initials: C
authors.lastname: Bordallo
authors.forename: Begoña
authors.initials: B
authors.lastname: Cantabrana
mesh_terms: 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
chemical_list: 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