TY - JOUR T1 - Dipyridamole inhibition of HCO3(-)-Cl- exchange in human erythrocytes. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 631 LP - 635 VL - 255 IS - 2 AU - T A Heming AU - C G Vanoye AU - A Bidani Y1 - 1990/11/01 UR - http://jpet.aspetjournals.org/content/255/2/631.abstract N2 - Effects of dipyridamole (DP) on Band 3-mediated HCO3(-)-Cl- exchange were investigated in human red cells at 37 degrees C. The kinetics of net HCO3(-)-Cl- exchange were monitored using a stopped-flow rapid reaction apparatus, under conditions in which HCO3(-)-Cl- exchange was rate-limiting for pH equilibration across the red cell membrane. DP was found to be a rapidly acting, potent inhibitor of HCO3(-)-Cl- exchange, with an apparent I50 of 4 microM. DP produced a mixed competitive-noncompetitive inhibition of HCO3-Cl- exchange. Greater than 50% of the inhibitory effect occurred within 20 msec of DP-red cell interaction, consistent with DP binding to an outward-facing site on the cell membrane. Interaction of red cells with DP was associated with a pH-dependent decrement in the equilibrium Donnan H+ ratio. Because HCO3(-)-Cl- exchange is crucial in vivo for ensuing rapid pH equilibration across the red cell membrane, these effects of DP may have important implications, particularly in the development of high-dose DP regimes for use as an adjunctive agent in cancer chemotherapy. ER -