Ca2+ binding and translocating properties of diflunisal.
We have characterized the binding of Ca2+ and Mg2+ to the anti-inflammatory drug diflunisal in acetonitrile and demonstrated the drug-mediated transport of Ca2+ across the lipid bilayer in unilamellar vesicles made of 1,2-dimyristoyl-sn-glycero-3-phosphocholine. Fluorescence and difference absorption spectral data show that diflunisal undergoes a significant conformational change on binding Ca2+ and Mg2+ forming, respectively, 1:2 and 1:1 cation:drug complexes with Kd in the low microM range. The kinetics of transport showed that Ca2+ was transported into the vesicle as 1:2 Ca2+:diflunisal sandwich complex. This suggests that the interaction of the drug with the cation in the lipid-mimetic solvent are similar. The biological relevance of the Ca(2+)-binding and translocating abilities of diflunisal is examined in light of the reported ionophoretic properties of several phospholipids as well as cyclooxygenase and lipoxygenase products.
Neigh
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GS
Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada.
Ananthanarayanan
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VS
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics*; D004061:Diflunisal / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004061:Diflunisal; D002118:Calcium