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We have studied the stereochemistry of accumulation of the hydrophilic beta-adrenoceptor antagonist rac-atenolol by human platelets in vitro. The accumulation was slow, not reaching equilibrium until 90 min at 37 degrees C. The uptake was temperature dependent with the accumulation at 37 degrees C being 3-4 times greater than at 4 degrees C. The accumulation was also stereoselective at 37 degrees C, favoring the active (-)-enantiomer over the (+)-enantiomer by 2.3-fold. Reserpine, but not desipramine, inhibited the platelet accumulation of rac-atenolol enantiospecifically. This uptake profile is different from the platelet uptake of lipophilic beta-blockers, which is characterized by nonspecific membrane binding, but similar to the carrier-mediated accumulation of the neurotransmitter norepinephrine by storage granules within the platelet.
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