Regulation of renal A(1) adenosine receptors in vivo.
We have compared renal A(1) adenosine receptor (AR) regulations in rats after chronic agonist and antagonist treatments. In one group, R-phenylisopropyladenosine (R-PIA), a selective A(1) AR agonist, was infused subcutaneously for 7 days. Another group was fed theophylline, a non-selective AR antagonist, for 2 weeks. Renal cortex membrane A(1) AR binding with 1,3-[(3)H]-dipropyl-8-cyclopentylxanthine demonstrated approximately 40% reduction in the B(max ) for the R-PIA group without any changes in the K(d) values. Neither the B(max) nor the K(d) changed following chronic theophylline treatment. Renal cortex G(i)alpha-proteins from the R-PIA treated rats decreased by approximately 30%. Renal G(i)alpha levels did not change in theophylline-treated rats. Consistent with the A(1) AR desensitization, R-PIA-treated rats had significantly higher basal renin release and showed attenuated A(1) AR-mediated inhibition of renin release. These data suggest that prolonged A(1) AR stimulation results in downregulation of renal A(1) ARs and G(i)alpha, accompanied by desensitization of A(1) AR-mediated inhibitory effects on renin release. Unlike cardiac and brain A(1) ARs, renal A(1) receptors are not subject to up-regulation following chronic antagonist treatment.
Lee
H Thomas
HT
Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA. tl128@columbia.edu
Cuomo-Scholer
Andrea
A
Belloni
Francis L
FL
Thompson
Carl I
CI
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism; D015151:Immunoblotting; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D012083:Renin / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology; D013997:Time Factors; D014970:Xanthines / Q000378:metabolism
D010726:Phosphodiesterase Inhibitors; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; D010660:Phenylisopropyladenosine; D013806:Theophylline; D012083:Renin; D019204:GTP-Binding Proteins; D000241:Adenosine