Source:http://linkedlifedata.com/resource/pubmed/id/18183621
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
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| pubmed:dateCreated |
2008-4-29
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| pubmed:abstractText |
Our previous study showed that YGGFMKKKFMRFamide (YFa), a chimeric peptide of Met-enkephalin, and Phe-Met-Arg-Phe-NH2 induced naloxone-reversible antinociception and attenuated the development of tolerance to morphine analgesia. In continuation, the present study investigated which specific opioid receptors-mu, delta or kappa-mediate the observed YFa antinociception pharmacologically using specific antagonists and whether chronic administration of YFa at 26.01 micromol/kg per day induces tolerance and its effect on the expression of mu and kappa opioid receptors from day 4 to day 6, with endomorphine-1 (EM-1) and saline taken as positive and negative controls, respectively. Quantitative differential expression analysis was carried out by real-time reverse-transcriptase polymerase chain reaction, and the corresponding changes in protein levels were assessed by Western blot. A pharmacological investigation revealed that nor-binaltorphimine, a specific kappa opioid receptor-1 (KOR1) antagonist, completely antagonized the antinociception induced by 39.01 micromol/kg of YFa. Importantly, its chronic intraperitoneal administration did not result in significant tolerance over 6 days, whereas EM-1 induced significant tolerance after day 4. Differential expression analysis revealed that EM-1 caused up-regulation of mu opioid receptor-1 on day 4, followed by down-regulation on later days. Interestingly, YFa treatment caused a decrease on day 4, followed by an increase in the expression of KOR1 from day 5 onward. In conclusion, YFa induces kappa-specific antinociception, with no development of tolerance during 6 days of chronic treatment, which further articulates new directions for improved designing of peptide-based analgesics that may be devoid of adverse effects like tolerance.
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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/Analgesics, Opioid,
http://linkedlifedata.com/resource/pubmed/chemical/Enkephalin, Methionine,
http://linkedlifedata.com/resource/pubmed/chemical/FMRFamide,
http://linkedlifedata.com/resource/pubmed/chemical/Met-enkephalin-FMRFa chimeric...,
http://linkedlifedata.com/resource/pubmed/chemical/Naltrexone,
http://linkedlifedata.com/resource/pubmed/chemical/Narcotic Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Opioid, kappa,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Opioid, mu,
http://linkedlifedata.com/resource/pubmed/chemical/endomorphin 1,
http://linkedlifedata.com/resource/pubmed/chemical/naltrindole,
http://linkedlifedata.com/resource/pubmed/chemical/norbinaltorphimine
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
1097-4547
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
15
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| pubmed:volume |
86
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1599-607
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| pubmed:meshHeading |
pubmed-meshheading:18183621-Analgesics, Opioid,
pubmed-meshheading:18183621-Analysis of Variance,
pubmed-meshheading:18183621-Animals,
pubmed-meshheading:18183621-Behavior, Animal,
pubmed-meshheading:18183621-Disease Models, Animal,
pubmed-meshheading:18183621-Dose-Response Relationship, Drug,
pubmed-meshheading:18183621-Drug Interactions,
pubmed-meshheading:18183621-Enkephalin, Methionine,
pubmed-meshheading:18183621-FMRFamide,
pubmed-meshheading:18183621-Gene Expression Regulation,
pubmed-meshheading:18183621-Male,
pubmed-meshheading:18183621-Naltrexone,
pubmed-meshheading:18183621-Narcotic Antagonists,
pubmed-meshheading:18183621-Oligopeptides,
pubmed-meshheading:18183621-Pain Measurement,
pubmed-meshheading:18183621-Rats,
pubmed-meshheading:18183621-Rats, Wistar,
pubmed-meshheading:18183621-Reaction Time,
pubmed-meshheading:18183621-Receptors, Opioid, kappa,
pubmed-meshheading:18183621-Receptors, Opioid, mu,
pubmed-meshheading:18183621-Time Factors
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| pubmed:year |
2008
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| pubmed:articleTitle |
YFa, a chimeric opioid peptide, induces kappa-specific antinociception with no tolerance development during 6 days of chronic treatment.
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| pubmed:affiliation |
Peptide Synthesis Laboratory, Institute of Genomics and Integrative Biology, Delhi, India.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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