Endogenous TRPV1 stimulation leads to the activation of the inositol phospholipid pathway necessary for sustained Ca2+ oscillations.

Abstract

Sensory neuron subpopulations as well as breast and prostate cancer cells express functional transient receptor potential vanilloid type 1 (TRPV1) ion channels; however little is known how TRPV1 activation leads to biological responses. Agonist-induced activation of TRPV1 resulted in specific spatiotemporal patterns of cytoplasmic Ca2+ signals in breast and prostate cancer-derived cells. Capsaicin (CAPS; 50μM) evoked intracellular Ca2+ oscillations and/or intercellular Ca2+ waves in all cell lines. As evidenced in prostate cancer Du 145 cells, oscillations were largely dependent on the expression of functional TRPV1 channels in the plasma membrane, phospholipase C activation and on the presence of extracellular Ca2+ ions. Concomitant oscillations of the mitochondrial matrix Ca2+ concentration resulted in mitochondria energization evidenced by increased ATP production. CAPS-induced Ca2+ oscillations also occurred in a subset of sensory neurons, yet already at lower CAPS concentrations (1μM). Stimulation of ectopically expressed TRPV1 channels in CAPS-insensitive NIH-3T3 cells didn't provoke CAPS-triggered Ca2+ oscillations; rather it resulted in low-magnitude, long-lasting elevations of the cytosolic Ca2+ concentration. This indicates that sole TRPV1 activation is not sufficient to generate Ca2+ oscillations. Instead the initial TRPV1-mediated signal leads to the activation of the inositol phospholipid pathway. This in turn suffices to generate a biologically relevant frequency-modulated Ca2+ signal.

• Authors: László Pecze, Walter Blum, Thomas Henzi, Beat Schwaller
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1863 Issue 12 Pg. 2905-2915 (12 2016) ISSN: 0006-3002 [Print] Netherlands
• PMID: 27663071 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• Diterpenes
• TRPV Cation Channels
• TRPV1 protein, human
• Inositol 1,4,5-Trisphosphate
• Adenosine Triphosphate
• resiniferatoxin
• Type C Phospholipases
• capsazepine
• Capsaicin
• Calcium

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Calcium (metabolism)
• Calcium Signaling
• Capsaicin (analogs & derivatives, pharmacology)
• Cell Line, Tumor
• Diterpenes (pharmacology)
• Gene Expression
• HEK293 Cells
• Humans
• Inositol 1,4,5-Trisphosphate (metabolism)
• Mice
• Mitochondria (drug effects, metabolism)
• NIH 3T3 Cells
• Primary Cell Culture
• Sensory Receptor Cells (cytology, drug effects, metabolism)
• TRPV Cation Channels (genetics, metabolism)
• Trigeminal Ganglion (cytology, drug effects, metabolism)
• Type C Phospholipases (genetics, metabolism)