cAMP efflux from human trophoblast cell lines: a role for multidrug resistance protein (MRP)1 transporter

Cyclic adenosine 3′-5′-monophosphate (cAMP) is a second messenger, which exerts an important role in the control of human first-trimester trophoblast functions. In the present study we demonstrate the existence of a mechanism that is able to extrude cAMP from trophoblast-derived cell lines, and show...

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Bibliographic Details
Published in:Molecular human reproduction 2010-07, Vol.16 (7), p.481-491
Main Authors: Biondi, C., Ferretti, M.E., Lunghi, L., Medici, S., Cervellati, F., Pavan, B., Vesce, F., Morano, D., Adinolfi, E., Bertoni, F., Abelli, L.
Format: Article
Language:English
Subjects:
adenosine
ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors
ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism
cAMP efflux
Cell Line, Tumor
Cells, Cultured
Colforsin - pharmacology
Cyclic AMP - metabolism
Estrone - pharmacology
Female
Fluorescent Antibody Technique
human trophoblast
Humans
In Vitro Techniques
Interleukin-1beta - pharmacology
MRP1
Placenta - metabolism
Pregnancy
Probenecid - pharmacology
Progesterone - pharmacology
Propionates - pharmacology
Quinolines - pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Trophoblasts - drug effects
Trophoblasts - metabolism
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Summary:Cyclic adenosine 3′-5′-monophosphate (cAMP) is a second messenger, which exerts an important role in the control of human first-trimester trophoblast functions. In the present study we demonstrate the existence of a mechanism that is able to extrude cAMP from trophoblast-derived cell lines, and show evidence indicating the involvement of multidrug resistance protein (MRP) 1, a transporter belonging to the ATP-binding cassette family, in cAMP egress. MRP1 is expressed in trophoblast cell lines and cAMP efflux is highly reduced by the MRP1 inhibitor, MK-571. In addition, interleukin-1β and estrone are able to enhance MRP1 gene expression and influence extracellular cAMP concentration. The occurrence of a MRP1-dependent cAMP efflux is also shown in human first-trimester placenta explants. Extracellular cAMP could represent a source for adenosine formation, which in turn could regulate cAMP-dependent responses in placental tissue. Evidence is provided that adenosine receptor subtypes are present and functional in human trophoblast-derived cells. A role for cAMP egress mechanism in the fine modulation of the nucleotide homeostasis is therefore suggested.
ISSN:1360-9947
1460-2407
DOI:10.1093/molehr/gaq023