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Avermectin transepithelial transport in MDR1- and MRP-transfected canine kidney monolayers.
- Source :
-
Veterinary research communications [Vet Res Commun] 2008 Jan; Vol. 32 (1), pp. 93-106. Date of Electronic Publication: 2007 Jun 20. - Publication Year :
- 2008
-
Abstract
- Fluxes of the anti-parasitic agents, [(3)H]-ivermectin, [(3)H]-selamectin and [(3)H]-moxidectin were studied across non-transfected and transfected canine kidney epithelial monolayers, MDCK II/wt, MDCK II-MDR1, MDCK II-MRP1 and MDCK II-MRP2. All four lines surprisingly expressed significant levels of P-glycoprotein (P-gp), coded for by MDR1, but MDCK II-MDR1 expressed increased levels compared to the other lines. MDCK II-MRP1 and MDCK II-MRP2 expressed increased levels of MRP1 and MRP2 respectively. Fluxes of [(3)H]-ivermectin, [(3)H]-selamectin, [(3)H]-moxidectin, and the P-gp substrates, rhodamine-123 and DiOC(2), were polarized in the basolateral-to-apical (secretory) direction across the four lines. Selected MRP inhibitors used in relevant pharmacological concentrations did not block the secretory fluxes of either [(3)H]-ivermectin or [(3)H]-selamectin in either the non-transfected or MRP-transfected lines. In contrast, secretory fluxes of ivermectin and selamectin were inhibited in all four lines by the P-gp inhibitor, verapamil. These data confirm that ivermectin and selamectin are substrates for P-gp in four additional cell lines, but suggest that they are not significant substrates for MRP1 or MRP2 where there is background expression of P-gp. Since this pattern of expression also pertains on the blood-brain barrier, it is unlikely that MRP1 and MRP2 play a significant role in ivermectin and selamectin blood: brain distribution in vivo.
- Subjects :
- Animals
Anthelmintics metabolism
Biological Transport
Cell Line
Dogs
Ivermectin metabolism
Kidney metabolism
Multidrug Resistance-Associated Protein 2
Multidrug Resistance-Associated Proteins metabolism
ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics
ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism
Ivermectin analogs & derivatives
Kidney cytology
Multidrug Resistance-Associated Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0165-7380
- Volume :
- 32
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Veterinary research communications
- Publication Type :
- Academic Journal
- Accession number :
- 17578674
- Full Text :
- https://doi.org/10.1007/s11259-007-9007-9