Linked Life Data

14602831

Source:http://linkedlifedata.com/resource/pubmed/id/14602831

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
31
pubmed:dateCreated
2003-11-6
pubmed:abstractText
Cell death mechanisms frequently involve the influx of extracellular calcium through voltage- and ligand-gated ion channels, e.g., the NMDA receptor (Greene, 1999). The vanilloid receptor (VR1) is present in regions of the brain (Mezey et al., 2000) that are highly susceptible to neurodegenerative insults, suggesting that this ion channel might contribute to the cellular processes involved in neuronal death. We tested the effects of VR1 ligands in the oxygen glucose deprivation (OGD) model of cell death in organotypic hippocampal slice cultures. The VR1 agonist capsaicin at concentrations that are selective for VR1 did not affect cell viability per se or the extent of neurodegeneration induced by the OGD insult. In contrast, the VR1 antagonist capsazepine (0.1-10 microm) significantly reduced the amount of OGD-induced cell death. However, capsazepine was still neuroprotective in slices prepared from VR1 knock-out mice, which exhibited the same degree of neurodegeneration to that observed in slices prepared from wild-type mice, excluding the possibility that it afforded neuroprotection through inhibition of VR1. Instead, capsazepine inhibited the hyperpolarization-activated nonspecific cation channel generated current I(h) in a concentration range similar to that which was neuroprotective. Furthermore, the specific I(h) blocker ZD-7288 was also neuroprotective, mirroring the effects of capsazepine, in that it was effective at preventing cell death when applied either during or after the OGD insult. These results demonstrate that capsazepine affords neuroprotection through inhibition of I(h) rather than inhibition of VR1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10146-53
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:14602831-Animals, pubmed-meshheading:14602831-Capsaicin, pubmed-meshheading:14602831-Cell Death, pubmed-meshheading:14602831-Cell Hypoxia, pubmed-meshheading:14602831-Cells, Cultured, pubmed-meshheading:14602831-Cyclic Nucleotide-Gated Cation Channels, pubmed-meshheading:14602831-Cytoprotection, pubmed-meshheading:14602831-Dose-Response Relationship, Drug, pubmed-meshheading:14602831-Glucose, pubmed-meshheading:14602831-Hippocampus, pubmed-meshheading:14602831-Ion Channels, pubmed-meshheading:14602831-Mice, pubmed-meshheading:14602831-Mice, Knockout, pubmed-meshheading:14602831-Nerve Tissue Proteins, pubmed-meshheading:14602831-Neurons, pubmed-meshheading:14602831-Neuroprotective Agents, pubmed-meshheading:14602831-Patch-Clamp Techniques, pubmed-meshheading:14602831-Potassium Channels, pubmed-meshheading:14602831-Rats, pubmed-meshheading:14602831-Rats, Sprague-Dawley, pubmed-meshheading:14602831-Receptors, Drug
pubmed:year
2003
pubmed:articleTitle
Capsazepine protects against neuronal injury caused by oxygen glucose deprivation by inhibiting I(h).
pubmed:affiliation
Neurology Centre of Excellence for Drug Discovery, GlaxoSmithKline, Harlow, Essex, CM19 5AW, United Kingdom. alison_m_ray@gsk.com
pubmed:publicationType
Journal Article, In Vitro