Nucleotides alter glucocorticoid receptor properties in an age-dependent manner.
The effects of various nucleotides on the binding of [3H] dexamethasone to rat liver cytosolic glucocorticoid receptors of various age groups were examined. In all the age groups studied (neonatal 4-10 days; adult, 45-60 days; and aged, 18-22 months), maximum receptor binding was obtained at 6 mM ATP concentration. At 6 mM ATP, binding was enhanced 20-100% (depending on the age groups) above controls. ADP was found to be as effective as ATP, whereas the effectiveness of other nucleotides was UTP greater than GTP greater than CTP. Interestingly, addition of any nucleotide to neonatal cytosol resulted in a higher binding of the hormone to receptor as compared to cytosols from the adult and aged animals. Although ATP or ADP added with 5 mM dithiothreitol gave optimum receptor binding for all of the 3 age groups tested, significantly higher hormone receptor binding was obtained upon addition of nucleotides plus dithiothreitol to cytosols from neonatal and aged rats as compared to adult rats. The time and temperature dependent inactivation of unbound glucocorticoid receptors was more effectively inhibited by addition of nucleotide plus dithiothreitol in aged animals than in neonatal and adult animals. This observation was used in the partial purification and characterization of hepatic glucocorticoid receptors from aged rats.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000375:Aging; D000818:Animals; D003080:Cold Temperature; D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D009711:Nucleotides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium
D009711:Nucleotides; D011965:Receptors, Glucocorticoid; D014316:Tritium; D003907:Dexamethasone; D000255:Adenosine Triphosphate; D004229:Dithiothreitol