title: The effect of isoprenaline and physical exertion to exhaustion on the mechanism of glucocorticoid action in the rat heart.
abstract: The effect of ATP and factors known to alter cellular ATP level on the properties of cytosolic glucocorticoid receptor of the heart were investigated. We measured the number of binding sites, binding affinity, receptor transformation and nuclear binding. Experiments performed on the cardiac cytosol of adrenalectomized rats labeled with hormone in vitro showed that both isoprenaline treatment and physical exertion to exhaustion decreased the number of triamcinolone acetonide binding sites, but had no significant effect on the binding affinity. Although ATP had an activating effect on the cytosolic steroid-receptor complexes, the results of phase partitioning and DEAE-cellulose chromatography indicated that neither isoprenaline nor exertion to exhaustion had any apparent effect on the equilibrium between the activated and unactivated forms of complexes. The amount of translocated complexes was dependent on the cytosolic receptor concentration. Experiments performed on the heart cytosol labeled with the hormone in vivo, showed that exertion to exhaustion changed the equilibrium between activated and unactivated complexes in favour of the latter form and at the same time decreased the amount of complexes bound to the nuclei and chromatin. It is not clear whether these changes reflect alterations in receptor activation and its accumulation in the nuclei, or whether they are connected with the release of the nuclear receptor due to the decrease in receptor affinity to chromatin or some other nuclear component. Speculatively, the data suggest that glucocorticoid action in heart cells may depend on the ability of cells to maintain a certain level of ATP.
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D005082:Physical Exertion; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism*; D014222:Triamcinolone Acetonide / Q000378:metabolism
chemical_list: D011965:Receptors, Glucocorticoid; D000255:Adenosine Triphosphate; D014222:Triamcinolone Acetonide; D007545:Isoproterenol