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Pharmacology of capsaicin-, anandamide-, and N-arachidonoyl-dopamine-evoked cell death in a homogeneous transient receptor potential vanilloid subtype 1 receptor population.
Br J Anaesth. 2010 May; 104(5):596-602.BJ

Abstract

BACKGROUND

Transient receptor potential vanilloid subtype 1 (TRPV1) receptor is a primary pain-sensing relay at peripheral sensory nerve endings and is also widespread in the brain, where it is implicated in neurodegeneration. Previous studies of TRPV1 neurotoxicity have utilized heterogeneous receptor populations, non-selective ligands, or non-neuronal cell types. Here, we explored the pharmacology of TRPV1-induced cytotoxicity in a homogeneous, neurone-like cellular environment.

METHODS

Cell death was examined in a human neurone-like cell line, stably expressing recombinant human TRPV1. Cytotoxicity was quantified in terms of nuclear morphology and mitochondrial complex II activity. Immunocytochemical markers of apoptotic cell death were also examined.

RESULTS

The TRPV1-selective agonist capsaicin, and the endovanilloids anandamide and N-arachidonoyl-dopamine (NADA), induced TRPV1-dependent delayed cell death in a concentration- and time-dependent manner. Capsaicin exposure time was significantly correlated with potency (r(2)=0.91, P=0.01). Release of cytochrome c from mitochondria, activation of caspase-3, and condensed nuclear chromatin were evident 6 h after capsaicin exposure, but cytotoxicity was unaffected by a pan-caspase inhibitor (zVAD-fmk, 50 microM).

CONCLUSIONS

We conclude that capsaicin, anandamide, and NADA can initiate TRPV1-dependent delayed cell death in neurone-like cells. This is an apoptosis-like process, but independent of caspase activity.

Authors+Show Affiliations

Division of Anaesthesia, Critical Care and Pain Management, Department of Cardiovascular Sciences (Pharmacology and Therapeutics Group), University of Leicester, Leicester Royal Infirmary, Leicester LE1 5WW, UK.No 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

20354008

Citation

Davies, J W., et al. "Pharmacology of Capsaicin-, Anandamide-, and N-arachidonoyl-dopamine-evoked Cell Death in a Homogeneous Transient Receptor Potential Vanilloid Subtype 1 Receptor Population." British Journal of Anaesthesia, vol. 104, no. 5, 2010, pp. 596-602.
Davies JW, Hainsworth AH, Guerin CJ, et al. Pharmacology of capsaicin-, anandamide-, and N-arachidonoyl-dopamine-evoked cell death in a homogeneous transient receptor potential vanilloid subtype 1 receptor population. Br J Anaesth. 2010;104(5):596-602.
Davies, J. W., Hainsworth, A. H., Guerin, C. J., & Lambert, D. G. (2010). Pharmacology of capsaicin-, anandamide-, and N-arachidonoyl-dopamine-evoked cell death in a homogeneous transient receptor potential vanilloid subtype 1 receptor population. British Journal of Anaesthesia, 104(5), 596-602. https://doi.org/10.1093/bja/aeq067
Davies JW, et al. Pharmacology of Capsaicin-, Anandamide-, and N-arachidonoyl-dopamine-evoked Cell Death in a Homogeneous Transient Receptor Potential Vanilloid Subtype 1 Receptor Population. Br J Anaesth. 2010;104(5):596-602. PubMed PMID: 20354008.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacology of capsaicin-, anandamide-, and N-arachidonoyl-dopamine-evoked cell death in a homogeneous transient receptor potential vanilloid subtype 1 receptor population. AU - Davies,J W, AU - Hainsworth,A H, AU - Guerin,C J, AU - Lambert,D G, Y1 - 2010/03/30/ PY - 2010/4/1/entrez PY - 2010/4/1/pubmed PY - 2010/5/14/medline SP - 596 EP - 602 JF - British journal of anaesthesia JO - Br J Anaesth VL - 104 IS - 5 N2 - BACKGROUND: Transient receptor potential vanilloid subtype 1 (TRPV1) receptor is a primary pain-sensing relay at peripheral sensory nerve endings and is also widespread in the brain, where it is implicated in neurodegeneration. Previous studies of TRPV1 neurotoxicity have utilized heterogeneous receptor populations, non-selective ligands, or non-neuronal cell types. Here, we explored the pharmacology of TRPV1-induced cytotoxicity in a homogeneous, neurone-like cellular environment. METHODS: Cell death was examined in a human neurone-like cell line, stably expressing recombinant human TRPV1. Cytotoxicity was quantified in terms of nuclear morphology and mitochondrial complex II activity. Immunocytochemical markers of apoptotic cell death were also examined. RESULTS: The TRPV1-selective agonist capsaicin, and the endovanilloids anandamide and N-arachidonoyl-dopamine (NADA), induced TRPV1-dependent delayed cell death in a concentration- and time-dependent manner. Capsaicin exposure time was significantly correlated with potency (r(2)=0.91, P=0.01). Release of cytochrome c from mitochondria, activation of caspase-3, and condensed nuclear chromatin were evident 6 h after capsaicin exposure, but cytotoxicity was unaffected by a pan-caspase inhibitor (zVAD-fmk, 50 microM). CONCLUSIONS: We conclude that capsaicin, anandamide, and NADA can initiate TRPV1-dependent delayed cell death in neurone-like cells. This is an apoptosis-like process, but independent of caspase activity. SN - 1471-6771 UR - https://www.unboundmedicine.com/medline/citation/20354008/Pharmacology_of_capsaicin__anandamide__and_N_arachidonoyl_dopamine_evoked_cell_death_in_a_homogeneous_transient_receptor_potential_vanilloid_subtype_1_receptor_population_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0007-0912(17)33619-X DB - PRIME DP - Unbound Medicine ER -