Abstract
Nociceptin/orphanin FQ (N/OFQ) and nocistatin (NST) are neuropeptides produced from the same precursor protein. N/OFQ is involved in a broad range of central functions including pain, learning, memory, anxiety, and feeding. However, NST has opposite effects on various central functions evoked by N/OFQ. The regulation of their receptors may be important for these opposite functions of NST and N/OFQ. Although N/OFQ binds to a specific N/OFQ receptor, the target molecule of NST remains unclear. Some biological effects of NST are mediated by a G protein-coupled receptor. Furthermore, using high-performance affinity nanobeads, we recently identified a 4-nitrophenylphosphatase domain and nonneuronal SNAP25-like protein homolog 1 (NIPSNAP1) as a protein that interacts with NST in the mouse spinal cord. The inhibition of N/OFQ-evoked tactile pain allodynia by NST is mediated by NIPSNAP1. This review focuses on the molecular mechanisms of pain regulation by the target molecules of NST including a G protein-coupled receptor and NIPSNAP1.
Keywords:
G protein-coupled receptor; NIPSNAP1; Nociceptin/orphanin FQ; Nocistatin; Nocistatin-interacting protein; Pain.
© 2015 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Drugs, Investigational / chemistry
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Drugs, Investigational / metabolism
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Drugs, Investigational / pharmacology*
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Drugs, Investigational / therapeutic use
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GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
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Humans
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Intercellular Signaling Peptides and Proteins
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Ligands
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Narcotic Antagonists / chemistry
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Narcotic Antagonists / metabolism
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Narcotic Antagonists / pharmacology*
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Narcotic Antagonists / therapeutic use
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Nerve Tissue Proteins / agonists
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Nerve Tissue Proteins / antagonists & inhibitors
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Nerve Tissue Proteins / metabolism*
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Neurons / drug effects*
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Neurons / metabolism
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Opioid Peptides / antagonists & inhibitors*
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Opioid Peptides / metabolism
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Pain / drug therapy
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Pain / metabolism
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Proteins / agonists
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Proteins / antagonists & inhibitors
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Proteins / metabolism*
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Receptors, Opioid / agonists
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Receptors, Opioid / chemistry
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Receptors, Opioid / metabolism*
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Synaptic Transmission / drug effects
Substances
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Drugs, Investigational
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Intercellular Signaling Peptides and Proteins
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Ligands
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NIPSNAP1 protein, human
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Narcotic Antagonists
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Nerve Tissue Proteins
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Opioid Peptides
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Proteins
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Receptors, Opioid
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nocistatin
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GTP-Binding Protein alpha Subunits, Gq-G11