Abstract |
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 ([Ca(2+)](i)). Our previous study demonstrated that Ca(2+)-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 [Ca(2+)](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 [Ca(2+)](i) in TRPM8-transfected human embryonic kidney cells (HEK293) but not in mock-transfected cells. Icilin and menthol induced Ca(2+) 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 [Ca(2+)](i) and NT secretion. The regulation of NT secretion in NETs by TRPM8 may have a potential clinical implication in diagnosis or therapy.
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Authors | Stefan Mergler, Mathias Z Strowski, Simone Kaiser, Thomas Plath, Yvonne Giesecke, Marleen Neumann, Hiroshi Hosokawa, Shigeo Kobayashi, Jan Langrehr, Peter Neuhaus, Ursula Plöckinger, Bertram Wiedenmann, Carsten Grötzinger |
Journal | Neuroendocrinology
(Neuroendocrinology)
Vol. 85
Issue 2
Pg. 81-92
( 2007)
ISSN: 0028-3835 [Print] Switzerland |
PMID | 17426390
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Pyrimidinones
- TRPM Cation Channels
- TRPM8 protein, human
- Menthol
- Neurotensin
- icilin
- Calcium
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Topics |
- Calcium
(metabolism)
- Humans
- Membrane Potentials
(drug effects)
- Menthol
(pharmacology)
- Models, Biological
- Neuroendocrine Tumors
(pathology)
- Neurotensin
(metabolism)
- Pancreatic Neoplasms
(pathology)
- Pyrimidinones
(pharmacology)
- TRPM Cation Channels
(agonists, metabolism)
- Tumor Cells, Cultured
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