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Transient receptor potential channel TRPM8 agonists stimulate calcium influx and neurotensin secretion in neuroendocrine tumor cells.
Neuroendocrinology. 2007; 85(2):81-92.N

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+Show Affiliations

Department of Internal Medicine, Division of Hepatology and Gastroenterology, Charité - Universitatsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany. stefan.mergler@charite.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17426390

Citation

Mergler, Stefan, et al. "Transient Receptor Potential Channel TRPM8 Agonists Stimulate Calcium Influx and Neurotensin Secretion in Neuroendocrine Tumor Cells." Neuroendocrinology, vol. 85, no. 2, 2007, pp. 81-92.
Mergler S, Strowski MZ, Kaiser S, et al. Transient receptor potential channel TRPM8 agonists stimulate calcium influx and neurotensin secretion in neuroendocrine tumor cells. Neuroendocrinology. 2007;85(2):81-92.
Mergler, S., Strowski, M. Z., Kaiser, S., Plath, T., Giesecke, Y., Neumann, M., Hosokawa, H., Kobayashi, S., Langrehr, J., Neuhaus, P., Plöckinger, U., Wiedenmann, B., & Grötzinger, C. (2007). Transient receptor potential channel TRPM8 agonists stimulate calcium influx and neurotensin secretion in neuroendocrine tumor cells. Neuroendocrinology, 85(2), 81-92.
Mergler S, et al. Transient Receptor Potential Channel TRPM8 Agonists Stimulate Calcium Influx and Neurotensin Secretion in Neuroendocrine Tumor Cells. Neuroendocrinology. 2007;85(2):81-92. PubMed PMID: 17426390.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transient receptor potential channel TRPM8 agonists stimulate calcium influx and neurotensin secretion in neuroendocrine tumor cells. AU - Mergler,Stefan, AU - Strowski,Mathias Z, AU - Kaiser,Simone, AU - Plath,Thomas, AU - Giesecke,Yvonne, AU - Neumann,Marleen, AU - Hosokawa,Hiroshi, AU - Kobayashi,Shigeo, AU - Langrehr,Jan, AU - Neuhaus,Peter, AU - Plöckinger,Ursula, AU - Wiedenmann,Bertram, AU - Grötzinger,Carsten, Y1 - 2007/04/05/ PY - 2006/12/15/received PY - 2007/02/22/accepted PY - 2007/4/12/pubmed PY - 2007/6/20/medline PY - 2007/4/12/entrez SP - 81 EP - 92 JF - Neuroendocrinology JO - Neuroendocrinology VL - 85 IS - 2 N2 - 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. SN - 0028-3835 UR - https://www.unboundmedicine.com/medline/citation/17426390/Transient_receptor_potential_channel_TRPM8_agonists_stimulate_calcium_influx_and_neurotensin_secretion_in_neuroendocrine_tumor_cells_ L2 - https://www.karger.com?DOI=10.1159/000101693 DB - PRIME DP - Unbound Medicine ER -