title: Receptor regulation of the volume-sensitive efflux of taurine and iodide from human SH-SY5Y neuroblastoma cells: differential requirements for Ca(2+) and protein kinase C.
abstract: The basal (swelling-induced) and receptor-stimulated effluxes of (125)I(-) 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 (125)I(-) (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 (125)I(-) 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 (125)I(-) and taurine under basal and receptor-stimulated conditions. Basal release of (125)I(-) and taurine was independent of Ca(2+) or the activity of protein kinase C (PKC). However, although PAR-1-stimulated taurine efflux was attenuated by either a depletion of intracellular Ca(2+) or inhibition of PKC by chelerythrine, the enhanced release of (125)I(-) was independent of both parameters. Stimulated efflux of (125)I(-) after activation of muscarinic cholinergic receptors was also markedly less dependent on Ca(2+) 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 (125)I(-) and taurine is differentially regulated by PKC activity and Ca(2+) availability.
authors.affiliation: Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109-0220, USA.
authors.forename: Tooba A
authors.initials: TA
authors.lastname: Cheema
authors.forename: Veryan A
authors.initials: VA
authors.lastname: Pettigrew
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Fisher
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D053119:Benzophenanthridines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D007454:Iodides / Q000378:metabolism*; D007457:Iodine Radioisotopes; D009447:Neuroblastoma; D009994:Osmolar Concentration; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D044463:Receptor, PAR-1 / Q000378:metabolism*; D013654:Taurine / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D053119:Benzophenanthridines; D007454:Iodides; D007457:Iodine Radioisotopes; D044463:Receptor, PAR-1; D013654:Taurine; C016299:chelerythrine; D011493:Protein Kinase C; D013917:Thrombin; D002118:Calcium