Renal adenosine A1 receptor binding characteristics and mRNA levels during the development of acute renal failure in the rat.

Abstract

1. The binding characteristics and mRNA levels for renal adenosine A1 receptors were investigated in normal rats and rats with acute renal failure (ARF) induced by either glycerol or HgCl2. 2. Saturation isotherms determined from the binding of [3H]-1,3-dipropyl-8-cyclopentylxanthine ([3H]-DPCPX), a selective adenosine A1 antagonist, to renal membranes of untreated rats gave values of 0.62 nM for the equilibrium dissociation constant (Kd) and 19.9 fmol mg-1 protein for the density of binding sites (Bmax). No saturable binding was observed with [3H]-2-(p-(carboxylethyl)-phenylethylamino)-5'-N-ethylcar box amido adenosine ([3H]-CGS 21680), a selective adenosine A2a agonist. 3. 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 Bmax and Kd for the binding of [3H]-DPCPX. No significant changes in the binding characteristics of [3H]-DPCPX were noted with membranes from rats 48 h following the production of ARF with HgCl2. 4. Adenosine A1 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 beta-actin at the same time points. No statistically significant changes in adenosine A1 receptor or beta-actin mRNA levels were noted 48 h after the induction of ARF with HgCl2. 5. This study indicates that glycerol-induced ARF in the rat is associated with an increase in renal adenosine A1 receptor density which appears to result from increased transcription of the gene for this receptor. An increase in adenosine A1 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.