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Identification of NIPSNAP1 as a nocistatin-interacting protein involving pain transmission.

4-Nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1) is a molecule of physiologically unknown function, although it is predominantly expressed in the brain, spinal cord, liver, and kidney. We identified NIPSNAP1 as a protein that interacts with the neuropeptide nocistatin (NST) from synaptosomal membranes of mouse spinal cord using high-performance affinity latex beads. NST, which is produced from the same precursor protein as an opioid-like neuropeptide nociceptin/orphanin FQ (N/OFQ), has opposite effects on pain transmission evoked by N/OFQ. The calculated full-length pre-protein of NIPSNAP1 was 33 kDa, whereas the N-terminal truncated form of NIPSNAP1 (29 kDa) was ubiquitously expressed in the neuronal tissues, especially in synaptic membrane and mitochondria of brain. The 29-kDa NIPSNAP1 was distributed on the cell surface, and NST interacted with the 29-kDa but not the 33-kDa NIPSNAP1. Although intrathecal injection of N/OFQ induced tactile allodynia in both wild-type and NIPSNAP1-deficient mice, the inhibition of N/OFQ-evoked tactile allodynia by NST seen in wild-type mice was completely lacking in the deficient mice. These results suggest that NIPSNAP1 is an interacting molecule of NST and plays a crucial role in pain transmission.

Pubmed ID: 22311985


  • Okuda-Ashitaka E
  • Minami T
  • Tsubouchi S
  • Kiyonari H
  • Iwamatsu A
  • Noda T
  • Handa H
  • Ito S


The Journal of biological chemistry

Publication Data

March 23, 2012

Associated Grants


Mesh Terms

  • Analgesics, Opioid
  • Animals
  • Brain
  • COS Cells
  • Cercopithecus aethiops
  • Humans
  • Hyperalgesia
  • Mice
  • Mitochondria
  • Nerve Tissue Proteins
  • Opioid Peptides
  • Pain
  • Proteins
  • Spinal Cord
  • Synaptic Membranes
  • Synaptic Transmission