Pharmacology of capsaicin-, anandamide-, and N-arachidonoyl-dopamine-evoked cell death in a homogeneous transient receptor potential vanilloid subtype 1 receptor population
| Autor: | David G. Lambert, A. H. Hainsworth, Christopher J. Guerin, J. W. Davies |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Agonist
Programmed cell death medicine.drug_class Polyunsaturated Alkamides Dopamine N-Arachidonoyl dopamine TRPV1 TRPV Cation Channels Apoptosis Arachidonic Acids Pharmacology chemistry.chemical_compound medicine Tumor Cells Cultured Humans Receptor Neurons Dose-Response Relationship Drug business.industry Anandamide Anesthesiology and Pain Medicine nervous system chemistry Capsaicin lipids (amino acids peptides and proteins) business Endocannabinoids |
| DOI: | 10.1093/bja/aeq067 |
| Popis: | 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 (r2=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 µM). 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. |
| Databáze: | OpenAIRE |
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