n-n-dimethylsphingenine and Brain-Neoplasms

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.

Topics: Brain Neoplasms; Calcium; Cell Line; Enzyme Inhibitors; GTP-Binding Proteins; Humans; Image Processing, Computer-Assisted; Inositol 1,4,5-Trisphosphate; Lysophospholipids; Methacholine Chloride; Muscarinic Agonists; N-Methylscopolamine; Neuroblastoma; Receptor, Muscarinic M3; Receptors, Muscarinic; Signal Transduction; Sphingosine