Chronic dipyridamole administration downregulates [3H]nitrobenzylthioinosine binding site affinity in guinea pig kidney but not heart and brain.

Specific binding of the nucleoside transporter probe, [3H]nitrobenzylthioinosine, ([3H]NBMPR) was measured in washed guinea pig cardiac, renal and forebrain membranes after 14 days of treatment with dipyridamole (37.5 mg/kg, s.c., b.i.d.) or vehicle. When compared to values in vehicle-treated animals, a 100 percent increase in equilibrium dissociation constant (Kd) was observed in the kidney of dipyridamole-treated animals (0.51 +/- 0.04 to 1.0 +/- 0.06, p < 0.01). The maximal binding capacity (Bmax) was unaltered. No changes were observed in the heart or forebrain. The increase in Kd suggests that chronic dipyridamole treatment decreases the apparent binding affinity of NBMPR for kidney nucleoside transporters. Cardiac and brain nucleoside transporters may be either less susceptible to chronic dipyridamole administration or have a different adaptive mechanism.