Regulation of Renal A₁ Adenosine Receptors in vivo

Abstract

We have compared renal A₁ adenosine receptor (AR) regulations in rats after chronic agonist and antagonist treatments. In one group, R-phenylisopropyladenosine (R-PIA), a selective A₁ AR agonist, was infused subcutaneously for 7 days. Another group was fed theophylline, a non-selective AR antagonist, for 2 weeks. Renal cortex membrane A₁ AR binding with 1,3-[³H]-dipropyl-8-cyclopentylxanthine demonstrated ∼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_iα-proteins from the R-PIA treated rats decreased by ∼30%. Renal G_iα levels did not change in theophylline-treated rats. Consistent with the A₁ AR desensitization, R-PIA-treated rats had significantly higher basal renin release and showed attenuated A₁ AR-mediated inhibition of renin release. These data suggest that prolonged A₁ AR stimulation results in downregulation of renal A₁ ARs and G_iα, accompanied by desensitization of A₁ AR-mediated inhibitory effects on renin release. Unlike cardiac and brain A₁ ARs, renal A₁ receptors are not subject to up-regulation following chronic antagonist treatment.

Experimental hypothyroidism modifies specific binding of A1 and A2A analogues to adenosine receptors in the rat kidney

“…It has been reported that in some conditions such as acute renal failure, the expression of A 1 adenosine receptors is increased in the renal cortex while reduced in the IM, which helps to explain the abnormalities in renal function ( Smith et al ., 2000 ). There is no clear explanation for these alterations in receptor expression, but mechanisms such as up and downregulation and G protein coupling may be involved ( Lee et al ., 2002 ). We could speculate that in hypothyroidism, thyroid hormone imbalance may induce changes in adenosine receptor expression in the kidney.…”

Renal tubule necrosis and apoptosis modulation by A1 adenosine receptor expression

“…3,5 Typical of G-protein-coupled receptors, A 1 AR density is subject to up-and downregulation: chronic agonist or antagonist stimulation leads to up or downregulation of A 1 ARs, respectively, in several organs including the kidney. [6][7][8] We have previously demonstrated that chronic treatments with a non-selective AR agonist abolished the protective effects of adenosine in a human proximal tubule cell line (HK-2) against hydrogen peroxide (H 2 O 2 )-mediated injury. 5 Moreover, chronic treatments with a non-selective AR antagonist in HK-2 cells increased the endogenous tolerance to H 2 O 2 .…”