Effect of dimethylsphingosine on muscarinic M(3) receptor signalling in SH-SY5Y cells.
The sphingosine kinase inhibitor, dimethylsphingosine, is an important tool for investigating intracellular effects of the putative second messenger compound, sphingosine 1-phosphate. However, the specificity of action of dimethylsphingosine has not been fully investigated. In human SH-SY5Y neuroblastoma cells, dimethylsphingosine (30 microM), produced a 25-fold increase in the EC(50) for methacholine-induced Ca(2+) mobilisation, and reduced the maximum response by 57+/-5%, suggesting the involvement of sphingosine 1-phosphate production in the Ca(2+) signal. However, dimethylsphingosine also inhibited [3H]N-methylscopolamine binding to whole SH-SY5Y cells and reduced methacholine-induced phosphoinositide turnover. Thus, this compound must be used with caution when investigating the role of sphingosine kinase in G-protein coupled receptor-mediated Ca(2+) mobilisation responses.
Young
K W
KW
Department of Cell Physiology and Pharmacology, Medical Sciences Building, University of Leicester, University Road, Leicester LE1 9HN, UK. kwy1@le.ac.uk
Channing
D R
DR
Nahorski
S R
SR
D001932:Brain Neoplasms / Q000378:metabolism; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D008246:Lysophospholipids; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D019832:N-Methylscopolamine / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000494:pharmacology
D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D018721:Muscarinic Agonists; C064769:N-acetylsphingosine; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic; D016210:Methacholine Chloride; C060506:sphingosine 1-phosphate; D015544:Inositol 1,4,5-Trisphosphate; D019204:GTP-Binding Proteins; C061800:N,N-dimethylsphingosine; D013110:Sphingosine; D002118:Calcium; D019832:N-Methylscopolamine