Source:http://linkedlifedata.com/resource/pubmed/id/15105221
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2004-4-23
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| pubmed:abstractText |
Although tramadol is widely available as an analgesic, its mechanism of antinociception remains unresolved. Serotonin (5-hydroxytryptamine, 5-HT) is a monoaminergic neurotransmitter that modulates numerous sensory, motor, and behavioral processes. The 5-HT type 2C receptor (5-HT(2C)R) is one of the major 5-HT receptor subtypes and is implicated in many important effects of 5-HT, including pain, feeding, and locomotion. In this study, we used a whole-cell voltage clamp to examine the effects of tramadol on 5-HT-induced Ca(2+)-activated Cl(-) currents mediated by 5-HT(2C)R expressed in Xenopus oocytes. Tramadol inhibited 5-HT-induced Cl(-) currents at pharmacologically relevant concentrations. The protein kinase C (PKC) inhibitor, bisindolylmaleimide I (GF109203x), did not abolish the inhibitory effects of tramadol on the 5-HT(2C)R-mediated events. We also studied the effects of tramadol on [(3)H]5-HT binding to 5-HT(2C)R expressed in Xenopus oocytes, and found that it inhibited the specific binding of [(3)H]5-HT to 5-HT(2C)R. Scatchard analysis of [(3)H]5-HT binding revealed that tramadol altered the apparent dissociation constant for binding without changing maximal binding, indicating competitive inhibition. The results suggest that tramadol inhibits 5-HT(2C)R function, and the mechanism of this inhibitory effect seems to involve competitive displacement of the 5-HT binding to the 5-HT(2C)R, rather than via activation of the PKC pathway. IMPLICATIONS: We examined the effects of tramadol on 5-hydroxytryptamine type 2C receptor (5-HT(2C)R) expressed in Xenopus oocytes. Tramadol inhibited 5-HT(2C)R function and the specific binding of [(3)H]5-HT to 5-HT(2C)R in a competitive manner. From these data, the mechanism of the inhibitory effect on 5-HT(2C)R might involve the competitive displacement of 5-HT binding to the 5-HT(2C)R.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Analgesics, Opioid,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Chloride Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Serotonin, 5-HT2C,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Tramadol
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
0003-2999
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
98
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1401-6, table of contents
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| pubmed:dateRevised |
2007-11-15
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| pubmed:meshHeading |
pubmed-meshheading:15105221-Analgesics, Opioid,
pubmed-meshheading:15105221-Animals,
pubmed-meshheading:15105221-Calcium,
pubmed-meshheading:15105221-Chloride Channels,
pubmed-meshheading:15105221-Enzyme Activation,
pubmed-meshheading:15105221-Microinjections,
pubmed-meshheading:15105221-Oocytes,
pubmed-meshheading:15105221-Protein Kinase C,
pubmed-meshheading:15105221-Rats,
pubmed-meshheading:15105221-Receptor, Serotonin, 5-HT2C,
pubmed-meshheading:15105221-Serotonin,
pubmed-meshheading:15105221-Serotonin Antagonists,
pubmed-meshheading:15105221-Tramadol,
pubmed-meshheading:15105221-Xenopus
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| pubmed:year |
2004
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| pubmed:articleTitle |
The inhibitory effects of tramadol on 5-hydroxytryptamine type 2C receptors expressed in Xenopus oocytes.
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| pubmed:affiliation |
Department of Anesthesiology, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Fukuoka 807-8555, Japan.
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| pubmed:publicationType |
Journal Article
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