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unlikely that the efficacy of AEDs in this study (non– P-gp substrates or weak P-gp substrates) was affected by P-gp expression at the blood-brain barrier in dogs. ABBREVIATIONS AED Antiepileptic drug P-gp P-glycoprotein a. Sigma
ATP-binding cassette drug transporters, such as P-gp. 1 P-glycoprotein is a membrane-bound efflux pump that is localized in tissues with a barrier function, such as the intestines, blood-brain barrier, bile canaliculi, and renal tubules. It is the
P-glycoprotein is a transmembrane efflux protein in the ATP-binding cassette family of transport proteins. It is encoded by the MDR1 gene, which is currently termed ABCB1 . Humans and dogs have only 1 form of the ABCB1 gene, whereas mice have
expression changes in p-glycoprotein (p-gp) observed in human dementia patients to CCD patients. To plot and quantify the longitudinal progression of behavioral deviations and biomarker values that pinpoint the onset of CCD. Achieving these goals in
to hypothesize that the administration of spinosad increases systemic exposure to ivermectin. It is known that there is increased systemic exposure to ivermectin in dogs with impaired P-glycoprotein function. 4 The most commonly known and examined
expression of the transfected vector from the expression of intrinsic P-gp because P-gp represents one of the natural defenses of most cells to toxic compounds. P-glycoprotein was strongly expressed 48 hours after transfection of the pLNC-cMDR1 clone into COS
overexpression in drug-resistant tumor cells, ABCB1 is primarily expressed in cells of intestinal, hepatic, renal, and brain tissue. 3,4,8–10 P-glycoprotein contributes to the barrier function of these organs and protects the cells by actively extruding
expressed in high concentrations on epithelial cells of the liver, renal tubules, and most secretory organs; the capillary endothelium of the bloodbrain and blood-testis barriers; and nodal lymphocytes. P-glycoprotein extrudes large, hydrophobic, uncharged
Abstract
Objective—To determine the frequency of the MDR1 gene mutation (polymorphism) associated with ivermectin sensitivity in a sample population of Collies in Washington and Idaho.
Animals—40 healthy client-owned Collies.
Procedure—A blood sample (8 ml) was collected from each dog and used for RNA extraction. Reverse transcriptase was used to generate MDR1 cDNA. Polymerase chain reaction (PCR) primers were designed to amplify a 1,061-base pair region of the MDR1 gene. The PCR products were sequenced to determine whether the Collies had 0, 1, or 2 mutant alleles. Pedigrees of some dogs were available for analysis to determine relatedness of affected dogs.
Results—Of the 40 Collies, 9 (22%) were homozygous for the normal allele (normal), 17 (42%) were heterozygous (carrier), and 14 (35%) were homozygous for the mutant allele (affected). Pedigree analysis revealed that some, but not all, affected dogs were related to each other within the 4 most recent generations.
Conclusions and Clinical Relevance—A high percentage of a sample population of Collies in Washington and Idaho are affected or carriers of the mutant MDR1 allele associated with ivermectin sensitivity. A similar frequency of this mutation may be detected in dogs from other geographic areas. Pharmacologic treatment with ivermectin, loperamide, vincristine, and other drugs that are substrates of P-glycoprotein, the MDR1 gene product, may result in neurologic toxicosis in a high percentage of Collies. (Am J Vet Res 2002;63:479–481)
