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Anti-nociceptive responses produced by human putative counterpart of nocistatin
Authors:Toshiaki Minami  Emiko Okuda-Ashitaka  Yuji Nishiuchi  Terutoshi Kimura  Shinro Tachibana  Hidemaro Mori  Seiji Ito
Affiliation:1.Department of Anesthesiology, Osaka Medical College, Takatsuki 569-8686, Japan;2.Department of Medical Chemistry, Kansai Medical University, Moriguchi 570-8506, Japan;3.Peptide Institute Inc., Protein Research Foundation, Minoh 562-0015, Japan;4.School of Biological Sciences, The National University of Singapore, Singapore 119260, Singapore
Abstract:b-nocistatin is a heptadecapeptide produced from bovine prepronociceptin and blocks the induction of hyperalgesia and touch-evoked pain (allodynia) by intrathecal administration of nociceptin or prostaglandin E2 (PGE2). Human prepronociceptin may generate a 30-amino acid peptide different in length from b-nocistatin. Here, we examine whether the human putative counterpart of nocistatin (h-nocistatin) possessed the same biological activities as b-nocistatin. Simultaneous intrathecal injection of h-nocistatin in mice blocked the induction of allodynia by nociceptin and PGE2 in a dose-dependent manner with ID50 values of 329 pg kg−1 and 16.6 ng kg−1, respectively. h-nocistatin was about 10 times less potent than b-nocistatin. h-nocistatin also attenuated the nociceptin- and PGE2-induced hyperalgesia. These results demonstrate that h-nocistatin is biologically active and may be involved in the processing of pain at the spinal level in humans.
Keywords:Nocistatin   nociceptin/orphanin FQ   prostaglandin E2   allodynia   hyperalgesia   spinal cord
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