Prostanoid receptors regulate the volume‐sensitive efflux of osmolytes from murine fibroblasts via a cyclic AMP‐dependent mechanism

Abstract

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 E1 (PGE1) potently (EC50 = 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 PGE1 to enhance taurine release. The ability of PGE1 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 PGE1 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). PGE1 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)