Identification and characterization of an endogenous ligand for opioid receptor homologue ROR-C: its involvement in allodynic response to innocuous stimulus.
We reported here purification and characterization of a novel heptadecapeptide in bovine brain as an endogenous ligand for ROR-C, an opioid receptor homologue cloned from rat cerebrum. The amino acid sequence of the peptide that we purified is identical to those recently identified as nociceptin in rat brain and orphanin FQ in porcine brain. The peptide inhibited the forskolin-induced cyclic AMP accumulation in ROR-C expressing Chinese hamster ovary cells. Studies on inhibitory activity of cyclic AMP accumulation and Northern blot analysis showed that the peptide and its precursor mRNA are present in a number of brain regions, less abundant in the spina cord, and negligible in the cerebellum. In situ hybridization analysis revealed that hybridization-positive neurons were distributed in the superficial layer (lamina I) of the dorsal horn and were also interspersed between the tract of Lissauer in the spinal cord. Intrathecal administration of the peptide into conscious mice induced allodynia, a pain response to innocuous tactile stimuli, in a beli-shaped manner. These results demonstrate that the peptide exists in the brain and spinal cord and plays an important role in pain transmission.
Okuda-Ashitaka
E
E
Department of Medical Chemistry, Kansai Medical University, Moriguchi, Japan.
Tachibana
S
S
Houtani
T
T
Minami
T
T
Masu
Y
Y
Nishi
M
M
Takeshima
H
H
Sugimoto
T
T
Ito
S
S
D000818:Animals; D001921:Brain / Q000378:metabolism; D016466:CHO Cells / Q000378:metabolism; D002417:Cattle; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D051379:Mice; D018847:Opioid Peptides / Q000378:metabolism*; D010146:Pain / Q000378:metabolism*; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D000097629:Nociceptin
D018847:Opioid Peptides; D011957:Receptors, Opioid; D000097629:Nociceptin