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 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-1beta 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.
Department of Biology and Evolution, Section of General Physiology, University of Ferrara, Ferrara, Italy.
C
C
Biondi
M E
ME
Ferretti
L
L
Lunghi
S
S
Medici
F
F
Cervellati
B
B
Pavan
F
F
Vesce
D
D
Morano
E
E
Adinolfi
F
F
Bertoni
L
L
Abelli
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004970:Estrone / Q000494:pharmacology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000494:pharmacology; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011339:Probenecid / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D053583:Interleukin-1beta; D011422:Propionates; D011804:Quinolines; D005576:Colforsin; D004970:Estrone; D011374:Progesterone; C059141:verlukast; D000242:Cyclic AMP; D011339:Probenecid