Potentiation of the osmosensitive release of taurine and D-aspartate from SH-SY5Y neuroblastoma cells after activation of M3 muscarinic cholinergic receptors

The ability of muscarinic cholinergic receptors (mAChRs) to regulate the volume-sensitive efflux of two organic osmolytes, namely, taurine and d-aspartate, from human SH-SY5Y neuroblastoma cells has been examined. Incubation of the cells with hypoosmolar buffers resulted in an efflux of both osmolyt...

Full description

Saved in:

Bibliographic Details
Published in:	The Journal of pharmacology and experimental therapeutics Vol. 311; no. 3; p. 1097
Main Authors:	Heacock, Anne M, Kerley, Daniel, Gurda, Grzegorz T, VanTroostenberghe, Aaron T, Fisher, Stephen K
Format:	Journal Article
Language:	English
Published:	United States 01-12-2004
Subjects:	Aspartic Acid - metabolism Cell Line, Tumor Dose-Response Relationship, Drug Enzyme Inhibitors - pharmacology Humans Ion Channels - antagonists & inhibitors Muscarinic Agonists - pharmacology Muscarinic Antagonists - pharmacology Neuroblastoma - metabolism Oxotremorine - pharmacology Phosphatidylinositols - metabolism Protein-Tyrosine Kinases - antagonists & inhibitors Protein-Tyrosine Kinases - metabolism Receptor, Muscarinic M3 - drug effects Receptor, Muscarinic M3 - metabolism Taurine - metabolism Water-Electrolyte Balance
Online Access:	Get more information
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The ability of muscarinic cholinergic receptors (mAChRs) to regulate the volume-sensitive efflux of two organic osmolytes, namely, taurine and d-aspartate, from human SH-SY5Y neuroblastoma cells has been examined. Incubation of the cells with hypoosmolar buffers resulted in an efflux of both osmolytes, with the threshold for release occurring at approximately 225 mOsM for taurine and d-aspartate. Inclusion of oxotremorine-M (Oxo-M), a muscarinic agonist, resulted in a marked enhancement of the volume-dependent efflux of both osmolytes and increased the threshold osmolarity for taurine and d-aspartate release to 340 (isotonic) and 320 mOsM, respectively. Maximum agonist stimulation of osmolyte release (350% of basal) was observed in the range of 225 to 250 mOsM. Oxo-M-stimulated osmolyte efflux was inhibited by muscarinic antagonists with a rank order of potency 4-diphenylacetoxy-N-methylpiperidine methiodide > pirenzepine > 11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one, a pharmacological profile identical to that obtained for M3 mAChR-stimulated phosphoinositide hydrolysis. Agonist-stimulated efflux of both osmolytes could be inhibited by inclusion of either anion channel blockers known to inhibit the volume-sensitive organic anion channel (VSOAC) or by a tyrosine kinase inhibitor alpha-cyano-(3,4-dihydroxy)cinnamonitrile. The results indicate that the activation of M3 mAChRs on SH-SY5Y neuroblastoma facilitates the ability of these cells to respond to very limited reductions in osmolarity via a release of osmolytes. mAChR-stimulated osmolyte efflux is mediated via a VSOAC and seems to require the activity of a tyrosine kinase.
ISSN:	0022-3565
DOI:	10.1124/jpet.104.072553