Possible involvement of endogenous nociceptin/orphanin FQ in the pain-related behavioral responses induced by its own metabolite, nociceptin/orphanin FQ(14-17).
Nociceptin/orphanin FQ(14-17) (N/OFQ(14-17)) is one of the major fragments that are released from N/OFQ, an endogenous ligand for the opioid receptor like-1 (ORL-1) receptor by endopeptidase 24.11. In the present study, we determined the pharmacological profiles of N/OFQ(14-17) on pain-related behavioral responses in the mouse. Intrathecal (i.t.) administration of N/OFQ(14-17) (5-160 pmol) evoked pain-related behaviors, and these behavioral responses were reduced by i.t. co-administration of an ORL-1 receptor antagonist, [Nphe(1)]N/OFQ(1-13)NH2 (4 pmol). However, in the ligand-binding receptor assay, N/OFQ(14-17) had no affinity for the ORL-1 receptor. Furthermore, i.t. pretreatment with an antiserum against N/OFQ (1:50) diminished the N/OFQ(14-17)-induced pain-related behaviors, suggesting that endogenous N/OFQ is involved in their expression. Therefore, N/OFQ(14-17)-induced pain-related behaviors may be mediated through the release of endogenous N/OFQ in the mouse spinal cord.
Watanabe
Hiroyuki
H
Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
Mizoguchi
Hirokazu
H
Orito
Tohru
T
Katsuyama
Sou
S
Yonezawa
Akihiko
A
Watanabe
Chizuko
C
Sakurada
Tsukasa
T
Sakurada
Shinobu
S
D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D008845:Microinjections; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D018847:Opioid Peptides / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D010146:Pain / Q000503:physiopathology* / Q000523:psychology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D000097629:Nociceptin
D006634:Histamine H1 Antagonists; D020319:Oligodeoxyribonucleotides, Antisense; D018847:Opioid Peptides; D010446:Peptide Fragments; D000097629:Nociceptin