Abstract
A neuropeptide nociceptin or orphanin FQ (N/OFQ) is an endogenous ligand for the orphan opioid receptor-like receptor. During studies on the analysis of the precursor of N/OFQ, we identified a novel neuropeptide produced from the same precursor and named it “nocistatin (NST)”. Intrathecal (i.t.) administration of N/OFQ induces pain responses including touch-evoked allodynia and thermal hyperalgesia, and simultaneous administration of NST blocks the allodynia and hyperalgesia induced by N/OFQ. In the years since these discoveries, N/OFQ has been shown to be involved in a wide range of pharmacological activities, such as relaying pain perception in peripheral tissues, to the central nervous system, and NST was shown to have opposite effects on various central functions evoked by N/OFQ. Pharmacological characterization using various neurotransmitter agents, agonists, antagonists and knockout mice in vivo; electrophysiological and immunohistological analysis ex vivo; and molecular cloning using affinity chromatography of high-performance affinity nanobeads; and protein processing measurement using bioluminescence resonance energy transfer (BRET) in vitro have generated new insights into pain transmission regulated by NST and N/OFQ. This review focuses on the molecular and cellular mechanisms of pain transmission regulated by NST.
Keywords: Pain, nocistatin, nociceptin/orphanin FQ, protein processing, synaptic transmission, central sensitization, neural network, receptor.
Current Pharmaceutical Design
Title:Nocistatin: Milestone of One Decade of Research
Volume: 21 Issue: 7
Author(s): Emiko Okuda-Ashitaka and Seiji Ito
Affiliation:
Keywords: Pain, nocistatin, nociceptin/orphanin FQ, protein processing, synaptic transmission, central sensitization, neural network, receptor.
Abstract: A neuropeptide nociceptin or orphanin FQ (N/OFQ) is an endogenous ligand for the orphan opioid receptor-like receptor. During studies on the analysis of the precursor of N/OFQ, we identified a novel neuropeptide produced from the same precursor and named it “nocistatin (NST)”. Intrathecal (i.t.) administration of N/OFQ induces pain responses including touch-evoked allodynia and thermal hyperalgesia, and simultaneous administration of NST blocks the allodynia and hyperalgesia induced by N/OFQ. In the years since these discoveries, N/OFQ has been shown to be involved in a wide range of pharmacological activities, such as relaying pain perception in peripheral tissues, to the central nervous system, and NST was shown to have opposite effects on various central functions evoked by N/OFQ. Pharmacological characterization using various neurotransmitter agents, agonists, antagonists and knockout mice in vivo; electrophysiological and immunohistological analysis ex vivo; and molecular cloning using affinity chromatography of high-performance affinity nanobeads; and protein processing measurement using bioluminescence resonance energy transfer (BRET) in vitro have generated new insights into pain transmission regulated by NST and N/OFQ. This review focuses on the molecular and cellular mechanisms of pain transmission regulated by NST.
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Cite this article as:
Okuda-Ashitaka Emiko and Ito Seiji, Nocistatin: Milestone of One Decade of Research, Current Pharmaceutical Design 2015; 21 (7) . https://dx.doi.org/10.2174/1381612820666141027112451
DOI https://dx.doi.org/10.2174/1381612820666141027112451 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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