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.