Sodium-dependent adenosine transport is diminished in brush border membrane vesicles from hypothyroid rat kidney

Studies of the uptake of [3H]adenosine ([3H]ADO) were performed using brush border membrane vesicles (BBMV) from normal (N) and hypothyroid (Tx) rat kidneys, to test if decreased Na+ reabsorption in hypothyroidism might be associated with abnormalities in ADO transport. [3H]ADO uptake (1-10 micromol) for both conditions was measured in the presence of Na+ (10-150 mmol/l); the effects of dipyridamole (10 micromol/l) and 1, 3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine (PACPX, 10 micromol/l) were also studied. Na+-stimulated ADO uptake was decreased in Tx BBMV. Michaelis-Menten constants showed a decreased ADO carrier affinity (Km 2.46 +/- 0.14 in N, vs Km 4.46 +/- 0.88 micromol/l in Tx, P<0.05), with no change in the number of carriers (Vmax 295 +/- 25 in N, vs 229.2 +/- 56 pmol.min-1.mg protein in Tx). Na+ affinity remained unchanged (K Na+ 11.5 +/- 3.5 in N, vs K Na+ 12.72 +/- 0.7 mmol/l in Tx). Inhibition of Na+-dependent ADO transport was 50% in N as opposed to 58% in Tx with dipyridamole, and 72% in N versus 47% in Tx with PACPX. These results suggest that decreased Na+-dependent ADO cotransport contributes to the diminished tubular reabsorption that occurs in hypothyroidism.