Interaction of mebendazole with tubulin from body wall muscle, intestine, and reproductive system of Ascaris suum.
The binding of tritiated mebendazole, a benzimidazole anthelmintic, to tubulin derived from intestine, body wall muscle, and reproductive system of adult Ascaris suum was examined and compared. Mebendazole binding was resolved into specific and nonspecific binding and the binding affinity (Ka) and maximum binding at infinite ligand concentration (Bmax) determined. Electron microscopy was performed to assess the tubulin in various tissues of A. suum quantitatively by observing the presence of microtubules. Total binding was highest in intestine followed by body wall muscle. It was least in the reproductive system. The intestine demonstrated greater specific binding per milligram of protein than the body wall muscle. However, in the reproductive system extract, high affinity binding was not detected. After correction for nonspecific binding of ligand, the results indicated that the Bmax of mebendazole for the tubulin of A. suum intestine was about 3-fold higher than for that of body wall muscle. The Ka of mebendazole for intestinal tubulin was similar to that for body wall muscle. Electron microscopy of A. suum tissues demonstrated that the tubulin content decreased from the intestine through the body wall muscle to the reproductive system. Differences in tubulin content from different tissues may determine the selective sensitivity of these tissues to benzimidazole attack.
Bughio
N I
NI
Institute of Parasitology, McGill University, Ste-Anne de Bellevue, Quebec, Canada.
Faubert
G M
GM
Prichard
R K
RK
D000818:Animals; D017165:Ascaris suum / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D005835:Genitalia / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000648:ultrastructure; D008463:Mebendazole / Q000378:metabolism* / Q000494:pharmacology; D008854:Microscopy, Electron; D008870:Microtubules / Q000648:ultrastructure; D009132:Muscles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D011485:Protein Binding; D013552:Swine; D014404:Tubulin / Q000378:metabolism*
D014404:Tubulin; D008463:Mebendazole