Intestinal tubulin as possible target for the chemotherapeutic action of mebendazole in parasitic nematodes
Abstract
In vitro incubation of the parasitic nematode Ascaris suum in the presence of 10 microM mebendazole (MBZ) resulted in a complete loss of colchicine binding ability of extracts obtained from the parasite's intestine. Biochemical evidence supported the identification of the colchicine binding receptor in A. suum intestinal extracts as tubulin. This protein was partially purified and found to comprise approximately 0.8% of the soluble intestinal protein. MBZ inhibited colchicine binding to the partially purified tubulin in a competitive manner, the inhibition constant being 4.22 X 10(-6) M. Colchicine binding to porcine brain tubulin was also competitively inhibited by MBZ, exhibiting an inhibition constant of 8.0 X 10(-6) M. [3H]Colchicine binding studies revealed an apparent association constant of A. suum tubulin of 5.88 X 10(4) M(-1). Similar experiments employing [3H]MBZ showed that the extent of MBZ binding to the tubulin up to 10(-5) M was linearly dependent on MBZ concentration. Due to solubility problems the precise association constant for MBZ could not be determined but is apparently less than 10(5) M(-1). In view of the small difference in drug binding abilities between nematode intestinal and mammalian brain tubulin i...Continue Reading
References
Citations
Related Concepts
Related Feeds
Ascariasis
Ascariasis is a helminthic infection of global distribution with more than 1.4 billion persons infected throughout the world. Here is the latest research.
Ascariasis (ASM)
Ascariasis is a helminthic infection of global distribution with more than 1.4 billion persons infected throughout the world. Here is the latest research.
Anthelmintics
Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.