QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.106.115741v1 320/3/1068    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cheema, T. A. Articles by Fisher, S. K. Search for Related Content PubMed PubMed Citation Articles by Cheema, T. A. Articles by Fisher, S. K.

NEUROPHARMACOLOGY

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

Molecular and Behavioral Neuroscience Institute (T.A.C., V.A.P., S.K.F.) and Department of Pharmacology (T.A.C., S.K.F.), University of Michigan, Ann Arbor, Michigan

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.

Address correspondence to: Dr. Stephen K. Fisher, University of Michigan, Molecular and Behavioral Neuroscience Institute, 5039 Biomedical Science Research Building, Ann Arbor, MI 48109-0220. E-mail: skfisher{at}umich.edu

This article has been cited by other articles:

				D. J. Foster, A. M. Heacock, R. F. Keep, and S. K. Fisher Activation of Muscarinic Cholinergic Receptors on Human SH-SY5Y Neuroblastoma Cells Enhances Both the Influx and Efflux of K+ under Conditions of Hypo-Osmolarity J. Pharmacol. Exp. Ther., May 1, 2008; 325(2): 457 - 465. [Abstract] [Full Text] [PDF]

				T. A. Cheema and S. K. Fisher Cholesterol Regulates Volume-Sensitive Osmolyte Efflux from Human SH-SY5Y Neuroblastoma Cells following Receptor Activation J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 648 - 657. [Abstract] [Full Text] [PDF]