Source:http://linkedlifedata.com/resource/pubmed/id/16676069
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2006-5-5
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pubmed:abstractText |
We recently demonstrated that antithrombin (AT) reduces ischemia/reperfusion (I/R)-induced liver injury in rats by increasing hepatic tissue levels of calcitonin gene-related peptide (CGRP), a neuropeptide released from the sensory nerve endings. In the present study, we examined the effect of AT on I/R-induced liver injury in wild type mice (CGRP+/+) and congenitally alphaCGRP-deficient mice (CGRP-/-). We also investigated any effects of AT on CGRP release from dorsal root ganglion neurons (DRG) isolated from CGRP+/+. Based on results obtained in the present study, we attempted to determine if the anti-inflammatory activity of AT in vivo is dependent mainly on sensory neuron activation. AT enhanced ischemia/reperfusion-induced increases in hepatic tissue levels of CGRP and 6-keto-PGF(1alpha), a stable metabolite of PGI2, in CGRP+/+, but it did not enhance these increases in CGRP-/-. AT inhibited reperfusion-induced increases in serum alanine aminotransferase levels by increasing hepatic tissue blood flow and by attenuating increases in hepatic levels of tumor necrosis factor and myeloperoxidase in CGRP+/+, although it showed neither of these therapeutic effects in CGRP-/-. AT increased CGRP release from cultured DRGs only in the presence of anandamide, and AT-induced increase in CGRP release was not observed in the presence KT5720, an inhibitor of protein kinase A (PKA). AT markedly increased intracellular levels of cAMP in the presence of anandamide. These results strongly suggest that AT might reduce I/R-induced liver injury by enhancing activation of the sensory neurons through activation of PKA in sensory neurons.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antithrombin III,
http://linkedlifedata.com/resource/pubmed/chemical/Calcitonin Gene-Related Peptide,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0340-6245
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
95
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
788-95
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:16676069-Animals,
pubmed-meshheading:16676069-Antithrombin III,
pubmed-meshheading:16676069-Blood Flow Velocity,
pubmed-meshheading:16676069-Calcitonin Gene-Related Peptide,
pubmed-meshheading:16676069-Cyclic AMP,
pubmed-meshheading:16676069-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:16676069-Ganglia, Spinal,
pubmed-meshheading:16676069-Liver,
pubmed-meshheading:16676069-Mice,
pubmed-meshheading:16676069-Mice, Knockout,
pubmed-meshheading:16676069-Neurons, Afferent,
pubmed-meshheading:16676069-Reperfusion Injury
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pubmed:year |
2006
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pubmed:articleTitle |
Antithrombin reduces reperfusion-induced liver injury in mice by enhancing sensory neuron activation.
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pubmed:affiliation |
Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto, Japan.
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pubmed:publicationType |
Journal Article
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