Abstract
We have compared renal A<sub>1</sub> adenosine receptor (AR) regulations in rats after chronic agonist and antagonist treatments. In one group, R-phenylisopropyladenosine (R-PIA), a selective A<sub>1</sub> 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<sub>1</sub> AR binding with 1,3-[<sup>3</sup>H]-dipropyl-8-cyclopentylxanthine demonstrated ∼40% reduction in the B<sub>max </sub> for the R-PIA group without any changes in the K<sub>d</sub> values. Neither the B<sub>max</sub> nor the K<sub>d</sub> changed following chronic theophylline treatment. Renal cortex G<sub>i</sub>α-proteins from the R-PIA treated rats decreased by ∼30%. Renal G<sub>i</sub>α levels did not change in theophylline-treated rats. Consistent with the A<sub>1</sub> AR desensitization, R-PIA-treated rats had significantly higher basal renin release and showed attenuated A<sub>1</sub> AR-mediated inhibition of renin release. These data suggest that prolonged A<sub>1</sub> AR stimulation results in downregulation of renal A<sub>1</sub> ARs and G<sub>i</sub>α, accompanied by desensitization of A<sub>1</sub> AR-mediated inhibitory effects on renin release. Unlike cardiac and brain A<sub>1</sub> ARs, renal A<sub>1</sub> receptors are not subject to up-regulation following chronic antagonist treatment.
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