| Nocistatin: a novel neuropeptide encoded by the gene for the nociceptin/orphanin FQ precursor. | |
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MedLine Citation:
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PMID: 10998544 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We identified a novel neuropeptide and named it "nocistatin." Its presence was expected by analysis of the precursor for the neuropeptide nociceptin or orphanin FQ (Noc/OFQ), previously identified as an endogenous ligand for the orphan opioid receptor-like receptor. The precursor prepronociceptin/orphanin FQ (ppNoc/OFQ) comprises at least two bioactive peptides, nocistatin and Noc/OFQ. Noc/OFQ is involved in a broad range of pharmacological actions in various tissues from the central nervous system to the periphery. In pain transmission, Noc/OFQ is reported to have different effects including nociception, no effect, and analgesia, depending on the animal species tested, doses, route of administration, and so on. We found that intrathecal administration of Noc/OFQ induced pain responses including allodynia and hyperalgesia. Simultaneous administration of nocistatin blocked the allodynia and hyperalgesia induced by Noc/OFQ, whereas anti-nocistatin antibody decreased the threshold for the Noc/OFQ-induced allodynia. The endogenous heptadecapeptide nocistatin was isolated from bovine brains and recently identified in mouse, rat, and human brain and in human cerebrospinal fluid. Although human, rat and mouse ppNoc/OFQ produced larger respective counterparts with 30, 35, and 41 amino acid residues, all peptides showed the antinociceptive activity. This activity was ascribed to the carboxyl-terminal hexapeptide of nocistatin, Glu-Gln-Lys-Gln-Leu-Gln, which is conserved beyond species. Nocistatin also attenuated the allodynia and hyperalgesia evoked by prostaglandin E(2) and the inflammatory hyperalgesia induced by formalin or carrageenan/kaolin, and reversed the Noc/OFQ-induced inhibition of morphine analgesia at picogram doses. Furthermore, nocistatin counteracted the impairment of learning and memory induced by Noc/OFQ or scopolamine. Nocistatin is widely present in the spinal cord and brain. Although nocistatin did not bind to the Noc/OFQ receptor, it bound to the membrane of mouse brain and spinal cord with a high affinity. Nocistatin is a novel bioactive peptide produced from the same precursor as Noc/OFQ, and it plays important roles in the regulation of pain transmission and learning and memory processes in the central nervous system. |
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Authors:
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E Okuda-Ashitaka; S Ito |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: Peptides Volume: 21 ISSN: 0196-9781 ISO Abbreviation: Peptides Publication Date: 2000 Jul |
Date Detail:
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Created Date: 2000-10-10 Completed Date: 2000-11-30 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8008690 Medline TA: Peptides Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1101-9 Citation Subset: IM |
Affiliation:
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Department of Medical Chemistry, Kansai Medical University, 10-15 Fumizono, 570-8506, Moriguchi, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Analgesics, Opioid / pharmacology Animals Brain / drug effects Cattle Cerebrospinal Fluid / drug effects Dose-Response Relationship, Drug Humans Learning / drug effects Memory / drug effects Mice Microscopy, Confocal Molecular Sequence Data Neuropeptides / genetics, pharmacology Opioid Peptides / chemistry, genetics*, pharmacology*, physiology* Rats Sequence Homology, Amino Acid Time Factors Vasodilator Agents / chemistry, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Analgesics, Opioid; 0/Neuropeptides; 0/Opioid Peptides; 0/Vasodilator Agents; 0/nociceptin; 0/nocistatin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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