Document Detail


Haemonchus contortus P-glycoprotein-2: in situ localization and characterization of macrocyclic lactone transport.
MedLine Citation:
PMID:  25486495     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Haemonchus contortus is a veterinary nematode that infects small ruminants, causing serious decreases in animal production worldwide. Effective control through anthelmintic treatment has been compromised by the development of resistance to these drugs, including the macrocyclic lactones. The mechanisms of resistance in H. contortus have yet to be established but may involve efflux of the macrocyclic lactones by nematode ABC transporters such as P-glycoproteins. Here we report the expression and functional activity of H. contortus P-glycoprotein 2 (Hco-PGP-2) expressed in mammalian cells and characterize its interaction with the macrocyclic lactones, ivermectin, abamectin and moxidectin. The ability of Hco-PGP-2 to transport different fluorophore substrates was markedly inhibited by ivermectin and abamectin in a dose-dependent and saturable way. The profile of transport inhibition by moxidectin was markedly different. Hco-PGP-2 was expressed in the pharynx, the first portion of the worm's intestine and perhaps in adjacent nervous tissue, suggesting a role for this gene in regulating the uptake of avermectins and in protecting nematode tissues from the effects of macrocyclic lactone anthelmintic drugs. Hco-PGP-2 may thus contribute to resistance to these drugs in H. contortus.
Authors:
Pablo Godoy; Jing Lian; Robin N Beech; Roger K Prichard
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-12-5
Journal Detail:
Title:  International journal for parasitology     Volume:  -     ISSN:  1879-0135     ISO Abbreviation:  Int. J. Parasitol.     Publication Date:  2014 Dec 
Date Detail:
Created Date:  2014-12-8     Completed Date:  -     Revised Date:  2014-12-9    
Medline Journal Info:
Nlm Unique ID:  0314024     Medline TA:  Int J Parasitol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014. Published by Elsevier Ltd.
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