RT Journal Article SR Electronic T1 Receptor Regulation of the Volume-Sensitive Efflux of Taurine and Iodide from Human SH-SY5Y Neuroblastoma Cells: Differential Requirements for Ca2+ and Protein Kinase C JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 1068 OP 1077 DO 10.1124/jpet.106.115741 VO 320 IS 3 A1 Tooba A. Cheema A1 Veryan A. Pettigrew A1 Stephen K. Fisher YR 2007 UL http://jpet.aspetjournals.org/content/320/3/1068.abstract AB The basal (swelling-induced) and receptor-stimulated effluxes of 125I- and taurine have been monitored to determine whether these two osmolytes are released from human SH-SY5Y cells under hypotonic conditions via common or distinct mechanisms. Under basal conditions, both 125I- (used as a tracer for Cl-) and taurine were released from the cells in a volume-dependent manner. The addition of thrombin, mediated via the proteinase-activated receptor-1 (PAR-1) subtype, significantly enhanced the release of both 125I- and taurine (3–6-fold) and also increased the threshold osmolarity for efflux of these osmolytes (“set-point”) from 200 to 290 mOsM. Inclusion of a variety of broad-spectrum anion channel blockers and of 4-[(2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]butanoic acid attenuated the release of both 125I- and taurine under basal and receptor-stimulated conditions. Basal release of 125I- and taurine was independent of Ca2+ or the activity of protein kinase C (PKC). However, although PAR-1-stimulated taurine efflux was attenuated by either a depletion of intracellular Ca2+ or inhibition of PKC by chelerythrine, the enhanced release of 125I- was independent of both parameters. Stimulated efflux of 125I- after activation of muscarinic cholinergic receptors was also markedly less dependent on Ca2+ availability and PKC activity than that observed for taurine release. These results indicate that, although the osmosensitive release of these two osmolytes from SH-SY5Y cells may occur via pharmacologically similar membrane channels, the receptor-mediated release of 125I- and taurine is differentially regulated by PKC activity and Ca2+ availability. The American Society for Pharmacology and Experimental Therapeutics