Dipyridamole inhibition of HCO3--Cl- exchange in human erythrocytes

T. A. Heming*, C. G. Vanoye, A. Bidani

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Effects of dipyridamole (DP) on Band 3-mediated HCO3--Cl- exchange were investigated in human red cells at 37°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 μM. 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.

Original languageEnglish (US)
Pages (from-to)631-635
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume255
Issue number2
StatePublished - Jan 1 1990

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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