Transient receptor potential channel TRPM8 agonists stimulate calcium influx and neurotensin secretion in neuroendocrine tumor cells.

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.

• 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)

Chemical References

• Pyrimidinones
• TRPM Cation Channels
• TRPM8 protein, human
• Menthol
• Neurotensin
• icilin
• Calcium

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