Transient Receptor Potential Channel TRPM8 Agonists Stimulate Calcium Influx and Neurotensin Secretion in Neuroendocrine Tumor Cells
| Autor: | Simone Kaiser, Carsten Grötzinger, Ursula Plöckinger, Mathias Z. Strowski, Marleen Neumann, Yvonne Giesecke, Bertram Wiedenmann, Hiroshi Hosokawa, Thomas Plath, Shigeo Kobayashi, Peter Neuhaus, Stefan Mergler, Jan M. Langrehr |
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| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism TRPM Cation Channels chemistry.chemical_element Pyrimidinones Calcium TRPC5 Models Biological Membrane Potentials Cellular and Molecular Neuroscience Transient receptor potential channel chemistry.chemical_compound Endocrinology Internal medicine Tumor Cells Cultured medicine TRPM8 Humans TRPM3 Neurotensin Ion channel Endocrine and Autonomic Systems Icilin Pancreatic Neoplasms Menthol Neuroendocrine Tumors chemistry |
| Zdroj: | Neuroendocrinology. 85:81-92 |
| ISSN: | 1423-0194 0028-3835 |
| DOI: | 10.1159/000101693 |
| Popis: | TRPM8 is a member of the melastatin-type transient receptor potential ion channel family. Activation by cold or by agonists (menthol, icilin) induces a transient rise in intracellular free calcium concentration ([Ca2+]i). Our previous study demonstrated that Ca2+-permeable cation channels play a role in IGF-1-induced secretion of chromogranin A in human neuroendocrine tumor (NET) cell line BON [Mergler et al.: Neuroendocrinology 2006;82:87–102]. Here, we extend our earlier study by investigating the expression of TRPM8 and characterizing its impact on [Ca2+]i and the secretion of neurotensin (NT). We identified TRPM8 expression in NET BON cells by RT-PCR, Western blotting and immunofluorescence staining. Icilin increased [Ca2+]i in TRPM8-transfected human embryonic kidney cells (HEK293) but not in mock-transfected cells. Icilin and menthol induced Ca2+ transients in BON cells as well as in primary NET cell cultures of two different pancreatic NETs as detected by single cell fluorescence imaging. Icilin increased non-selective cation channel currents in BON cells as detected by patch-clamp recordings. This activation was associated with increased NT secretion. Taken together, this study demonstrates for the first time the expression TRPM8 in NET cells and its role in regulating [Ca2+]i and NT secretion. The regulation of NT secretion in NETs by TRPM8 may have a potential clinical implication in diagnosis or therapy. |
| Databáze: | OpenAIRE |
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