Intracellular cAMP Increases During the Positive Inotropism Induced by Androgens in Isolated Left Atrium of Rat

Eur J Pharmacol. 2002 Mar 1;438(1-2):45-52. doi: 10.1016/s0014-2999(02)01300-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Adrenergic beta-Agonists / pharmacology
  • Adrenergic beta-Antagonists / pharmacology
  • Androgens / pharmacology*
  • Animals
  • Atenolol / pharmacology
  • Atrial Function
  • Binding, Competitive / drug effects
  • Cattle
  • Cyclic AMP / metabolism*
  • Dihydroalprenolol / metabolism
  • Dihydrotestosterone / chemistry
  • Dihydrotestosterone / pharmacology
  • Dose-Response Relationship, Drug
  • Heart Atria / drug effects*
  • Heart Atria / metabolism
  • In Vitro Techniques
  • Isoproterenol / pharmacology
  • Male
  • Membranes / drug effects
  • Membranes / metabolism
  • Myocardial Contraction / drug effects*
  • Phosphodiesterase Inhibitors / pharmacology
  • Rats
  • Rats, Wistar
  • Reserpine / pharmacology
  • Serum Albumin, Bovine / chemistry
  • Serum Albumin, Bovine / pharmacology
  • Tritium

Substances

  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Androgens
  • Phosphodiesterase Inhibitors
  • Dihydrotestosterone
  • Tritium
  • Serum Albumin, Bovine
  • Atenolol
  • Dihydroalprenolol
  • Reserpine
  • Cyclic AMP
  • Isoproterenol
  • 1-Methyl-3-isobutylxanthine