CHRONIC DIPYRIDAMOLE ADMINISTRATION DOWN-REGULATES [H-3] NITROBENZYLTHIOINOSINE BINDING-SITE AFFINITY IN GUINEA-PIG KIDNEY BUT NOT HEART AND BRAIN

Specific binding of the nucleoside transporter probe, [H-3]nitrobenzyl thioinosine, ([H-3]NBMPR) was measured in washed guinea pig cardiac, r enal and forebrain membranes after 14 days of treatment with dipyridam ole (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 dissoci ation 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 bindin g capacity (Bmax) was unaltered. No changes were observed in the heart or forebrain. The increase in Kd suggests that chronic dipyridamole t reatment decreases the apparent binding affinity of NBMPR for kidney n ucleoside transporters. Cardiac and brain nucleoside transporters may be either less susceptible to chronic dipyridamole administration or h ave a different adaptive mechanism.