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Prostanoid receptors regulate the volume‐sensitive efflux of osmolytes from murine fibroblasts via a cyclic AMP‐dependent mechanism
Author(s) -
Foster Dan,
Heacock Anne M.,
Fisher Stephen K.
Publication year - 2007
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.21.6.a795-a
Subject(s) - osmolyte , taurine , chemistry , receptor , protein kinase a , adenylyl cyclase , efflux , microbiology and biotechnology , biochemistry , biology , kinase , amino acid
The ability of prostanoid receptors to regulate the volume‐dependent efflux of taurine from murine fibroblasts (L cells) via a cAMP‐dependent mechanism has been examined. Incubation of L cells under hypoosmotic conditions resulted in a time‐dependent efflux of taurine, the threshold of release occurring at 250 mOsM. Addition of prostaglandin E 1 (PGE 1 ) potently (EC 50 = 2.5 nM) enhanced the efflux of taurine and increased the threshold for osmolyte release to 290 mOsM. Inclusion of agents known to inhibit volume‐sensitive organic osmolyte and anion channels blocked the ability of PGE 1 to enhance taurine release. The ability of PGE 1 to increase osmolyte release from L cells was mimicked by the addition of agents that inhibit cAMP breakdown, directly activate adenylyl cyclase, or are cell‐permeant analogs of cAMP. Taurine release elicited by either PGE 1 or 8‐(4‐chlorophenylthio)‐cAMP was attenuated by >70% in L cells that had been stably transfected with a mutant regulatory subunit of cAMP‐dependent protein kinase (PKA). PGE 1 stimulation of taurine efflux was not attenuated by either depletion of intracellular calcium or inhibition of protein kinase C. The results indicate that activation of prostanoid receptors on murine fibroblasts enhances osmolyte release via a cAMP and PKA‐dependent mechanism. Supported by NIH NS23831(SKF) and NIH Training Grant GM 07767(DJF)