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Dear colleagues,
We are working on permeation across caco-2 monolayers of a toxin which
is involved with apical uptake by OATP's (passive facilitated
transport), phase II metabolism and efflux by pumps (all mechanisms
were identified in Liver).
We would like to do some experiments to discriminate these mechanisms
in the intestinal barrier in vitro.
An ATP depletion will disturb pGP functionality but will it disturb
metabolism and OATP's as well?
An experiment at 4*c instead of 37*c will disturb metabolism but will
it disturb OATP's ?
Thank you for your help.
Jerome HENRI
Post doctoral fellow in Kinetics
Genetic Toxicology of Food Contaminants Unit
Laboratory for Studies and Research on Veterinary Drugs ans
Disinfectants
French Food Safety Agency - Fougeres
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he following message was posted to: PharmPK
Dear Jerome,
An ATP depletion should not disturb OATPs, as the driving force for
SLC transporters is cosubstrate gradient.
An experiment at 4C instead of 37C will disturb OATPs as the active
protein activity is optimal at physiological temperature and highly
disturb at 4C. However at this temperature you will also highly
disturb passive permeability, and any other active transport process
including Pgp.
Different transport mechanisms than the ones observed in the liver
could be present in the intestine. If your goal is to identify those
mechanisms, in the absence of specific inhibitors, you should go for
in vitro system overexpressing single transporters.
I hope this helps,
Kind regards
Dr. Agnes Poirier
Drug transport lab
DMPK, Roche-Basel
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And what is the driver for an antiport or synport system??
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