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MRP4 and MRP5 in the ciliary epithelium of the eye and their potential role in regulating extracellular cAMP levels
Author(s) -
Hotchkiss Adam G,
Pasumarthi Kishore,
CocaPrados Miguel,
Pelis Ryan M
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.732.3
Subject(s) - extracellular , intracellular , probenecid , ibmx , pharmacology , adenosine , microbiology and biotechnology , chemistry , endocrinology , stimulation , medicine , biology , forskolin
The purpose was to determine if the ciliary epithelium expresses multidrug resistance‐associated proteins (MRPs) that transport cyclic nucleotides, and if their activity can influence extracellular cAMP levels. MRP4 and MRP5 were detected in human ciliary body by microarray. mRNAs (RT‐PCR) for both transporters were also detected in a human ciliary epithelial (CE) cell line. Activity for MRP4/5 in CE cells was assessed using monochlorobimaneglutathione. The intracellular accumulation of monochlorobimaneglutathione increased dose‐dependently in the presence of the MRP inhibitors: indomethacin, probenecid, ibuprofen and furosemide. Treatment of CE cells with isoproterenol (100 μM) and IBMX (500 μM) increased intracellular cAMP levels 4.8‐fold (4.1 to 19.7 pmoles/10 6 cells) and extracellular cAMP 5.8‐fold (2.7 to 15.6 nM). The β‐adrenergic stimulation of extracellular cAMP levels was reduced 27–46% by ibuprofen, furosemide and probenecid (500 μM each), whereas indomethacin (500 μM) nearly prevented it completely (94%). MRP4/MRP5 activity may play an important role in aqueous humor dynamics through modulation of the extracellular cAMP‐adenosine signaling pathway. Funding: CIHR, NSERC and NIH.