Drug-binding properties of rat alpha 1-foetoprotein. Binding of warfarin, phenylbutazone, azapropazone, diazepam, digitoxin and cholic acid.
As part of an investigation into whether alpha 1-foetoprotein (alpha 1-FP) plays the same transport role in foetal serum as albumin does in the adult, the binding properties of both proteins were compared with respect to the binding of a series of compounds known to be bound by albumin's specific drug-binding sites. The binding of warfarin, phenylbutazone, azapropazone, diazepam, digitoxin and cholic acid by rat alpha 1-FP and serum albumin was studied by equilibrium dialysis at 4 degrees C. Rat alpha 1-FP was shown to have neither albumin's high-affinity site II (diazepam as marker) nor its site III (digitoxin and cholic acid as markers). High-affinity binding by alpha 1-FP was found for the specific markers (warfarin, phenylbutazone, azapropazone) of albumin's drug-binding site I. However, instead of albumin's one high-affinity site/molecule, a mean value of 0.5 site/molecule was obtained with rat alpha 1-FP. Charcoal treatment at neutral pH of rat serum albumin did not affect its measured binding properties, but treatment of the alpha 1-FP led to an increased affinity for warfarin, phenylbutazone and azapropazone without a change in the measured number of sites, indicating competition for binding at this site by (an) endogenous ligand(s). These results are discussed in terms of the structures of the two proteins and with respect to the physiological implications of the differences found.
D000818:Animals; D001032:Apazone / Q000378:metabolism; D001665:Binding Sites; D002606:Charcoal; D019826:Cholic Acid; D002793:Cholic Acids / Q000378:metabolism; D003975:Diazepam / Q000378:metabolism; D004074:Digitoxin / Q000378:metabolism; D010653:Phenylbutazone / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism; D014859:Warfarin / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism*
D002793:Cholic Acids; D012709:Serum Albumin; D000509:alpha-Fetoproteins; D002606:Charcoal; D014859:Warfarin; D004074:Digitoxin; D019826:Cholic Acid; D010653:Phenylbutazone; D001032:Apazone; D003975:Diazepam