Linked Life Data

11145977

Source:http://linkedlifedata.com/resource/pubmed/id/11145977

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-1-23
pubmed:abstractText
Excessive glutamatergic neurotransmission, particularly when mediated by the N:-methyl-D-aspartate (NMDA) subtype of glutamate receptor, is thought to underlie neuronal death in a number of neurological disorders. Histamine has been reported to potentiate NMDA receptor-mediated events under a variety of conditions. In the present study we have utilized primary hippocampal neurone cultures to investigate the effect of mast cell-derived, as well as exogenously applied, histamine on neurotoxicity evoked by excessive synaptic activity. Exposure of mature cultures for 15 min to an Mg(2+)-free/glycine-containing buffer to trigger synaptic transmission through NMDA receptors, caused a 30-35% neuronal loss over 24 h. When co-cultured with hippocampal neurones, activated mast cells increased excitotoxic injury to 60%, an effect that was abolished in the presence of histaminase. Similarly, addition of histamine during magnesium deprivation produced a concentration-dependent potentiation (+ 60%; EC(50) : 5 microM) of neuronal death which was inhibited by sodium channel blockers and NMDA receptor antagonists, although this effect did not involve known histamine receptors. The histamine effect was further potentiated by acidification of the culture medium. Cultures 'preconditioned' by sublethal (5 min) Mg(2+) deprivation exhibited less neuronal death than controls when exposed to a more severe insult. NMDA receptor activation and the extracellular regulated kinase cascade were required for preconditioning neuroprotection. The finding that histamine potentiates NMDA receptor-mediated excitotoxicity may have important implications for our understanding of conditions where enhanced glutamatergic neurotransmission is observed in conjunction with tissue acidification, such as cerebral ischaemia and epilepsy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
76
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
47-55
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11145977-Age Factors, pubmed-meshheading:11145977-Animals, pubmed-meshheading:11145977-Binding Sites, pubmed-meshheading:11145977-Cell Count, pubmed-meshheading:11145977-Cells, Cultured, pubmed-meshheading:11145977-Coculture Techniques, pubmed-meshheading:11145977-Drug Synergism, pubmed-meshheading:11145977-Drug Tolerance, pubmed-meshheading:11145977-Excitatory Amino Acid Antagonists, pubmed-meshheading:11145977-Hippocampus, pubmed-meshheading:11145977-Histamine, pubmed-meshheading:11145977-Ischemic Preconditioning, pubmed-meshheading:11145977-Magnesium, pubmed-meshheading:11145977-Mast Cells, pubmed-meshheading:11145977-Mitogen-Activated Protein Kinase Kinases, pubmed-meshheading:11145977-N-Methylaspartate, pubmed-meshheading:11145977-Neurons, pubmed-meshheading:11145977-Rats, pubmed-meshheading:11145977-Rats, Sprague-Dawley, pubmed-meshheading:11145977-Receptors, Histamine, pubmed-meshheading:11145977-Synapses, pubmed-meshheading:11145977-Synaptic Transmission, pubmed-meshheading:11145977-Tetrodotoxin
pubmed:year
2001
pubmed:articleTitle
Potentiation by histamine of synaptically mediated excitotoxicity in cultured hippocampal neurones: a possible role for mast cells.
pubmed:affiliation
Department of Neuroscience Research, SmithKline Beecham Pharmaceuticals, Harlow, UK. Stephen_Skaper-1@sbphrd.com
pubmed:publicationType
Journal Article