Renal adenosine A 1 receptor binding characteristics and mRNA levels during the development of acute renal failure in the rat

The binding characteristics and mRNA levels for renal adenosine A 1 receptors were investigated in normal rats and rats with acute renal failure (ARF) induced by either glycerol or HgCl 2 . Saturation isotherms determined from the binding of [ 3 H]‐1,3‐dipropyl‐8‐cyclopentylxanthine ([ 3 H]‐DPCPX), a selective adenosine A 1 antagonist, to renal membranes of untreated rats gave values of 0.62 n m for the equilibrium dissociation constant ( K d ) and 19.9 fmol mg −1 protein for the density of binding sites (B max ). No saturable binding was observed with [ 3 H]‐2‐(p‐(carboxylethyl)‐phenylethylamino)‐5′‐N‐ethylcarboxamido adenosine ([ 3 H]‐CGS 21680), a selective adenosine A 2a agonist. By contrast to time‐matched controls, renal membranes obtained from rats 16 and 48 h following the induction of ARF with glycerol, showed statistically significant increases (2–4 fold) in both B max and K d for the binding of [ 3 H]‐DPCPX. No significant changes in the binding characteristics of [ 3 H]‐DPCPX were noted with membranes from rats 48 h following the production of ARF with HgCl 2 . Adenosine A 1 receptor mRNA levels were significantly elevated 0.5, 16 and 48 h following induction of ARF with glycerol, whilst no change was noted in mRNA levels for β‐actin at the same time points. No statistically significant changes in adenosine A 1 receptor or β‐actin mRNA levels were noted 48 h after the induction of ARF with HgCl 2 . This study indicates that glycerol‐induced ARF in the rat is associated with an increase in renal adenosine A 1 receptor density which appears to result from increased transcription of the gene for this receptor. An increase in adenosine A 1 receptor density in renal resistance vessels may explain, at least in part, the enhanced renal vasoconstrictor response to adenosine in glycerol‐induced ARF that was noted in a previous study.British Journal of Pharmacology (1997) 120 , 947–953; doi: 10.1038/sj.bjp.0700980