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

I Binding kinetic studies with the adenosine analogues [H-3]CPA (0.250-50 nM) and [H-3]CGS21680 (0.1-100nM) were performed in renal tissue from control (NL) and thyroidectomised (HTX) rats. We propose that the low renal adenosine content reported in hypothyroid rats may induce changes in the density and/or affinity of adenosine receptor, distributed in the cortex (C), outer medulla (OM), and inner medulla (IM) of the kidney. 2 [H-3]CPA and [H-3]CGS21680 binding saturation isotherms were fitted by nonlinear regression analysis and evaluated by Furchgott's method. These results revealed high (K-H) and low (K-L) affinity (K-D) sites for both compounds. As expected, a heterogeneous pattern was observed for B-max and K-D values. 3 Bound [H-3]CPA and [H-3]CGS21680 were displaced by increasing concentrations of nonlabelled DPCPX and NECA, respectively, indicating the presence of A(1) and A(2A) adenosine receptors distributed in the renal segments studied. 4 The relative intrinsic efficacy (8) for [H-3]CPA and [H-3]CGS21680 showed extreme values (far from 1.0), 0.5 in IM NL and 2.70 in IM HTX for [H-3]CGS21680. 5 Our results indicate that A(2A) adenosine receptor is predominant in IM from HTX, but A, receptors are expressed preferentially in C in NL. 6 We conclude that the changes observed in number, affinity, and epsilon for the A(2A) receptor in IM from HTX might be responsible from alterations in medullary function, that is, incapacity for urine concentration as observed in the hypothyroid kidney.