Re: MK571 and CFDA

From: Ronald Rabin (rr84g@nih.gov)
Date: Wed Apr 24 2002 - 14:19:01 EST


Bryone, CFDA appears, according to Molecular Probes to be pumped out faster
than other dyes (calcein) used for MRP assessment.  I am assuming you are
loading with the acetoxymethyl ester (5-CFDA-AM).  If you are not, the anion
will not get into the cell.  If you are loading with the succinic ester,
that is a tracking dye that binds to cell proteins and tracks cell division.
I would use calcein AM, and that loads well with HBSS.  In the ester form,
however, these probes are pumped out by MDR at the membrane before they
actually enter the cytoplasm and are broken down by esterases.  If your
cells have variable expression of MDR, that may account for variablity in
loading.  In that case,  load in the presence of verapamil, 10 ug/ml, then
wash out the verapamil.

MD571 is, at higher concentrations necessary than LTC4 receptor inhibition,
an MRP1 inhibitor.

ron

on 4/23/02 3:48 AM, Bryone Kuss at bryone.kuss@flinders.edu.au wrote:

> Dear All,
>
> We have been having problems with the transport of CFDA in functional assays
> of MRP1.
>
> PBS+gluc is the recommended solution for the assay but our cells do not like
> it and die rather quickly. The effects of using Hanks in place of this were to
> significantly reduce the transport of CFDA out of the cells, although the
> cells were much healthier. Alternatively there is a creatine and Tris buffered
> PBS solution but we have not tried this.
> What do others find?
>
> Secondly, we have found that MK571 works unreliably as an inhibitor of MRP1 in
> media + FCS. Does anyone have any experience they would be willing to share
> about either of these agents?
>
> Many thanks, Bryone
>
> Bryone J Kuss
>
> MBBS, PhD
> Department of Haematology and Genetic Pathology
> FMC, Flinders University
> South Australia 5042
>
> Fax  618 8204 5450
>

Ronald L. Rabin, M.D.
Senior Staff Fellow
Laboratory of Immunobiochemistry
DBPAP/OVRR
Center for Biologics Evaluation and Research
U.S. Food and Drug Administration
29 Lincoln Drive (MSC-4555)
Building 29, Room 129
Bethesda, MD   20892-4555

phone:  301.496.8806
fax:    301.402.5177
email:  rr84g@nih.gov



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