In vitro inhibitory effects of J-113397 on nociceptin/orphanin FQ-stimulated [S-35]GTP gamma S binding to mouse brain

Citation
D. Ichikawa et al., In vitro inhibitory effects of J-113397 on nociceptin/orphanin FQ-stimulated [S-35]GTP gamma S binding to mouse brain, NEUROREPORT, 12(8), 2001, pp. 1757-1761
Citations number
20
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
NEUROREPORT
ISSN journal
0959-4965 → ACNP
Volume
12
Issue
8
Year of publication
2001
Pages
1757 - 1761
Database
ISI
SICI code
0959-4965(20010613)12:8<1757:IVIEOJ>2.0.ZU;2-E
Abstract
J-113397 (1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethy l-1,3-dihydro-2H-benzimidazol-2-one) is a recently developed antagonist of the opioid receptor-like 1 (ORL1) receptor. We compared the in vitro functi onal profile of J-113397 on [S-35]guanosine 5'-O-(gamma -thio)triphosphate (GTP gammaS) binding to mouse brain with that of [Phe(1)Psi (CH2NH)Gly(2)]n ociceptin(1-13)NH2 and naloxone benzoylhydrazone (Na1BzoH). J-113397 antago nized nociceptin/orphanin FQ-stimulated [S-35]GTP gammaS binding to mouse b rain with an 1C(50) value of 7.6 nM, but had no effect on basal [S-35]GTP g ammaS binding by itself. [Phe(1)Psi (CH2-NH)Gly(2)]nociceptin(1-13)NH2 part ially antagonized nociceptin/orphanin FQ-stimulated [S-35]GTP gammaS bindin g but showed agonistic activity on ORL1 by itself. Na1BzoH showed antagonis tic activity on ORL1 receptor but had significant agonistic activity on oth er opioid receptors at lower doses. Schild plot analysis demonstrated compe titive antagonism of J-113397 on ORL1 receptor in mouse brain. A [S-35]GTP gammaS binding study using ORL1 receptor-deficient mice confirmed the selec tive antagonism of J-113397 on ORL1 receptor. These data indicate that J-11 3397 is the most potent and selective antagonist of ORL1 receptor in mouse brain that has yet been reported, and therefore will be a useful tool for c haracterization of ORL1 receptors in the brain. NeuroReport 12:1757-1761 (C ) 2001 Lippincott Williams & Wilkins.