Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nociceptin/orphanin FQ (N/OFQ) is a 17-amino acid endogenous neuropeptide ligand for the nociceptin receptor (NOP). We have prepared a [(3)H]-labelled truncated N/OFQ peptide, [(3)H]N/OFQ(1-13)NH(2) and compared its binding characteristics with [(3)H]N/OFQ(1-17)OH and [(125)I]Y(14)N/OFQ(1-17)OH in membranes prepared from Chinese hamster ovary cells expressing the recombinant human NOP (CHO(hNOP)) and the rat cerebrocortex. [(3)H]N/OFQ(1-13)NH(2), [(3)H]N/OFQ(1-17)OH and [(125)I]Y(14)N/OFQ(1-17)OH binding to CHO(hNOP) was concentration dependent and saturable with receptor density (B(max)) and radioligand equilibrium dissociation constant (pK(d)) values (mean +/- SEM) of 1043 +/- 58 fmol/mg protein and 10.35 +/- 0.03, 1348 +/- 44 fmol/mg protein and 10.06 +/- 0.04, and 1169 +/- 76 fmol/mg protein and 10.45 +/- 0.06, respectively. In the rat, B(max) and pK(d) values for [(3)H]N/OFQ(1-13)NH(2) and [(3)H]N/OFQ(1-17)OH were 130 +/- 1 fmol/mg protein and 10.70 +/- 0.03, and 157 +/- 4 fmol/mg protein and 10.34 +/- 0.02, respectively. The binding of all radioligands was displaced by a range of peptide and non-peptide ligands. There was a strong correlation (r(2) = 0.92, P = 0.002) between pK(i) values estimated with [(3)H]N/OFQ(1-13)NH(2) and [(3)H]N/OFQ(1-17)OH. No such correlation was observed in comparison with the [(125)I]-labelled peptide (poor agreement with low affinity N/OFQ(1-9)NH(2), Dynorphin-A and Naloxone benzoylhydrazone). We suggest that [(3)H]N/OFQ(1-13)NH(2) may be a useful alternative to [(3)H]N/OFQ(1-17)OH.
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PMID:Comparison of the binding of [(3)H]nociceptin/orphaninFQ(1-13)NH(2), [(3)H]nociceptin/orphaninFQ(1-17)OH and [(125)I]Tyr(14)nociceptin/orphaninFQ(1-17)OH to recombinant human and native rat cerebrocortical nociceptin/orphanin FQ receptors. 1212 46

The neuropeptide nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the nociceptin receptor (NOP). In an attempt to identify high potency NOP agonists for use in the brain we have compared the activity of a novel N/OFQ analogue [Phe(1)Psi(CH(2)-O)Gly(2)]N/OFQ(1-13)NH(2) ([F/G-O]) with the existing [Phe(1)Psi(CH(2)-NH)Gly(2)]N/OFQ(1-13)NH(2) ([F/G]). Both peptides are modified between the first two N-terminal amino acids and are further compared with the agonist template N/OFQ(1-13)NH(2) in [(3)H]N/OFQ binding, GTPgamma[(35)S] binding and cAMP inhibition studies using Chinese hamster ovary cells expressing the recombinant human NOP. All peptides displaced [(3)H]N/OFQ, stimulated GTPgamma[(35)S] binding and inhibited cAMP formation. In [(3)H]N/OFQ binding and GTPgamma[(35)S] binding the rank order affinity and potency was N/OFQ(1-13)NH(2)>[F/G-O]>[F/G]. In GTPgamma[(35)S] binding [F/G] was a clear partial agonist with intrinsic activity (E(max) stimulation factor, mean+/-SEM, n=4) of 7.75+/-1.02 compared with N/OFQ(1-13)NH(2) of 11.13+/-1.76. The efficacy of [F/G-O] (10.17+/-1.88) approached that of the full agonist N/OFQ(1-13)NH(2). Downstream, at the level of cAMP formation, all peptides were full agonists with the following rank order potency: N/OFQ(1-13)NH(2)>[F/G-O]=[F/G]. The enhanced potency and intrinsic activity of the novel [F/G-O] modification makes this an interesting peptide for further in vivo analysis.
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PMID:Assessment of the activity of a novel nociceptin/orphanin FQ analogue at recombinant human nociceptin/orphanin FQ receptors expressed in Chinese hamster ovary cells. 1285 5