Specific interaction of ivermectin with retinol-binding protein from filarial parasites.
Specific cellular binding proteins for retinol and retinoic acid from mammalian and avian species may mediate the action of retinoids in the control of epithelial differentiation, growth and tumorigenesis. Parasite retinol-binding protein (PRBP) and parasite retinoic acid-binding protein (PRABP) isolated and characterized from parasitic worms of the family Filarioidea might be involved in some possible action of vitamin A compounds in these parasites. Ivermectin, a potent and widely used anti-parasitic drug, competes efficiently with retinol for retinol-binding sites on PRBP, but not for the host-tissue retinol-binding-protein sites. The drug has no affinity for retinoic acid-binding proteins from either parasite or host tissues. Binding studies using radiolabelled ivermectin and retinol reveal that ivermectin has a higher affinity than retinol for PRBP. A correlation exists between the binding affinities of ivermectin analogues and their anti-parasitic activities. A binding-protein-mediated interrelationship may exist between the actions of retinol and ivermectin in the parasites, but not in the host tissues.
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Kettering-Meyer Laboratory, Southern Research Institute, Birmingham, AL 35255-5305.
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D000818:Animals; D002499:Centrifugation, Density Gradient; D005370:Filarioidea / Q000378:metabolism*; D007559:Ivermectin / Q000378:metabolism*; D009854:Onchocerca / Q000378:metabolism; D051381:Rats; D012177:Retinol-Binding Proteins / Q000378:metabolism*; D013045:Species Specificity; D014018:Tissue Distribution; D014801:Vitamin A / Q000378:metabolism
D012177:Retinol-Binding Proteins; D014801:Vitamin A; D007559:Ivermectin