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Hi All,
In the real practice, do you include wild type MDCK (WT-MDCK) every time when you run P-gp assay to identify a P-gp substrate or inhibitor? I understand that WT-MDCK is used as a control to rule out the impact of canine P-gp on drug transport in MDR1-MDCK cell monolayer. However, is there any evidence to show the substrate spetrum difference for human and canine P-gp? How much benefit and certainty will be gained with the inclusion of WT-MDCK in the study? Actually, this will double the workload, particularly in the inhibitor assay. Any input is highhly appreciated.
Huadong
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Hi Huadong,
It all depends on what you are looking in a compound.
a) If you want a quick answer, like in discovery mode, bidirectional transport may be good for Pgp substrate or prediction of human blood brain barrier permeability whereas digoxin with and without compound is good for Pgp inhibition.
b) If you are looking for more detailed information like development mode or role of other transporters or canine Pgp then you may want to include both wild and transfected cell lines.
c) There is a nice paper published by Stina et al in DMD, 2009 which showed more than 80% amino acid homology between dog and human Pgp but I am not sure functionally, are there any differences in the substrates?
Also, I have a question to the group members.
Did anybody look into the differences between the functionality of MDR1-MDCK cells originated from Netherlands Cancer Institute vs NIH? Any insight would be really appreciated.
Thanks,
Raj
Rajinder Bhardwaj
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HI Rajinder,
Thanks a lot for your reply. I am also curious about the difference between MDR1-MDCK from NIH and MDR1-MDCK from Netherland Cancer Institute.
Huadong
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