• HOME
• New Product and Technology
• Nocistatin – Novel peptide from the prepronociceptin precursor!

Nocistatin – Novel peptide from the prepronociceptin precursor!  

[A peptide that blocks nociceptin action is found from the nociceptin precursor]

Nociceptin[Nature, 377, 532 (1995)]/ Orphanin FQ[Science, 270, 792 (1995)], a recently discovered peptide, is an endogenous ligand for the orphan opioid-like receptor. Nociceptin induces both allodynia (pain resulting from a non-noxious stimulus to normal skin) and hyperalgesia when administered intrathecally[Brit. J. Pharmacol., 121, 401 (1997)].

Bovine nocistatin: Nocistatin, a 17-residue peptide, which is encoded upstream from nociceptin in the cDNA sequence, was isolated from bovine brain[Nature, 392, 286 (1998)]. Surprisingly, these co-translated peptides show opposite biological effects: nocistatin blocks the nociceptin induced allodynia and hyperalgesia. Nocistatin also attenuated pain responses evoked by prostaglandin E₂. Nocistatin binds to the membrane of mouse brain and spinal cord with a high affinity but does not bind to the nociceptin receptor. Nocistatin and nociceptin may play opposite roles in pain transmission. The finding of nocistatin should be of great interest to the field of pain research and opioid pharmacology, and may lead to the design of a novel analgesic devoid of the addiction and dependence seen in morphine.

Human nocistatin: Bovine nocistatin is flanked by a pair of basic residues and is a 17-residue peptide, while the human precursor lacks the corresponding amino-terminal double basic residues and may be processed enzymatically to a 30-residue peptide. This putative peptide was synthesized chemically and was found to have the same biological activities as bovine nocistatin[Br. J. Pharmacol., 124, 1016 (1998)]. The IC₅₀ values are one order of magnitude higher than those of the bovine peptide; however, the efficacy is still high enough as an endogenous pharmacological agent. Therefore, this peptide is termed human nocistatin, which may be involved in the modulation of pain transmission in humans.

Print this page