The beta-adrenergic transduction system in kidneys from young and senescent rats.
beta-Adrenoceptor density, ligand affinity, high-affinity agonist binding, basal adenylate cyclase activity and cAMP synthesis upon stimulation with either forskolin, F-, guanine nucleotides (GTP or GppNHp) or isoproterenol in the presence of the nucleotides were studied in membranes prepared from kidneys of young (2-3 month) and old (24-25 month) male Wistar rats. There is a significant (P less than 0.01) 62% increase in beta-receptor density, a significant (P less than 0.05) 115% decrease in ligand affinity, a significant (P less than 0.05) 33% decrease of high-affinity binding sites for (-)-isoproterenol and a significant (P less than 0.01) 151% decrease of the affinity of the high-affinity agonist binding site. Basal adenylate cyclase activity and the activity after stimulation with guanine nucleotides and forskolin were significantly higher in old animals as compared to young (P less than 0.01). Stimulation of the system with isoproterenol in the presence of GTP was more effective in old animals, although the P less than 0.05 level of significance was barely reached. It is suggested that age-dependent changes of the beta-adrenoceptors in rat kidney are similar to those described for lungs: changes at the different levels of the beta-adrenergic transduction chain associated with age are compensatory so as to ensure equal cAMP synthesis for a given agonist stimulation.
Vanscheeuwijck
P
P
Heymans Institute of Pharmacology, University of Ghent Medical School, Belgium.
Van de Velde
E
E
Fraeyman
N
N
D000067956:Adenylyl Cyclase Inhibitors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008790:Metoprolol / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives; D011412:Propanolamines / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D000067956:Adenylyl Cyclase Inhibitors; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D006165:Guanylyl Imidodiphosphate; C026777:ICI 118551; D020120:Iodocyanopindolol; D010869:Pindolol; D000242:Cyclic AMP; D008790:Metoprolol; D007545:Isoproterenol