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Transient receptor potential channel TRPM8 agonists stimulate calcium influx and neurotensin secretion in neuroendocrine tumor cells.
- Source :
-
Neuroendocrinology [Neuroendocrinology] 2007; Vol. 85 (2), pp. 81-92. Date of Electronic Publication: 2007 Apr 05. - Publication Year :
- 2007
-
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.
- Subjects :
- Humans
Membrane Potentials drug effects
Models, Biological
TRPM Cation Channels metabolism
Tumor Cells, Cultured
Calcium metabolism
Menthol pharmacology
Neuroendocrine Tumors pathology
Neurotensin metabolism
Pancreatic Neoplasms pathology
Pyrimidinones pharmacology
TRPM Cation Channels agonists
Subjects
Details
- Language :
- English
- ISSN :
- 0028-3835
- Volume :
- 85
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Neuroendocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 17426390
- Full Text :
- https://doi.org/10.1159/000101693