PMID- 10484077
OWN - NLM
STAT- MEDLINE
DCOM- 19990917
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 58
IP  - 7
DP  - 1999 Oct 1
TI  - Profound differences in the transport of steroids by two mouse P-glycoproteins.
PG  - 1191-9
AB  - There are two mouse P-glycoproteins that convey multidrug resistance, mdr1 
      (mdr1b) and mdr3 (mdr1a), by serving as drug efflux transporters. These proteins 
      each exhibit tissue-specific expression. There is relatively high expression of 
      the mdr1 gene in the adrenals, the site of glucocorticoid and mineralocorticoid 
      hormone synthesis. We previously demonstrated that mdr1 gene expression in murine 
      thymoma cells correlated well with a decrease in their ability to accumulate the 
      glucocorticoid dexamethasone and their increased resistance to 
      glucocorticoid-induced apoptosis. Additional evidence is presented that supports 
      the proposition that the mdr1 P-glycoprotein can transport glucocorticoids. 
      Specifically, introduction and expression of the mouse mdr1 gene in the human HEK 
      293T cell line conveys a multidrug resistance phenotype that includes a reduced 
      capacity to accumulate dexamethasone. Moreover, isolation of additional 
      mdr1-expressing mouse lymphoid cells, without using steroids in the selection, 
      confirms the linkage between multidrug resistance conveyed by the mdr1 
      P-glycoprotein and resistance to dexamethasone. In contrast, two newly isolated 
      lymphoid lines, selectively expressing the mdr3 gene, were not found to have 
      increased dexamethasone resistance or the capacity to accumulate significantly 
      lower levels of hormone. The results support the concept that the mdr1 and mdr3 
      P-glycoproteins may serve alternative roles in the transport of endogenous 
      substances such as steroids.
FAU - Gruol, D J
AU  - Gruol DJ
AD  - The Sidney Kimmel Cancer Center, San Diego, CA 92121, USA. dgruol@skcc.org
FAU - Vo, Q D
AU  - Vo QD
FAU - Zee, M C
AU  - Zee MC
LA  - eng
GR  - DK51107/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B/genetics/*metabolism
MH  - Animals
MH  - Anti-Inflammatory Agents/metabolism
MH  - Biological Transport
MH  - Dexamethasone/*metabolism
MH  - Drug Interactions
MH  - Drug Resistance
MH  - Female
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Tumor Cells, Cultured
EDAT- 1999/09/14 00:00
MHDA- 1999/09/14 00:01
CRDT- 1999/09/14 00:00
PHST- 1999/09/14 00:00 [pubmed]
PHST- 1999/09/14 00:01 [medline]
PHST- 1999/09/14 00:00 [entrez]
AID - S0006295299002014 [pii]
AID - 10.1016/s0006-2952(99)00201-4 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1999 Oct 1;58(7):1191-9. doi: 10.1016/s0006-2952(99)00201-4.