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

Ichikawa, Daisuke; Ozaki, Satoshi; Azuma, Tomoko; Nambu, Hirohide; Kawamoto, Hiroshi; Iwasawa, Yoshikazu; Takeshima, Hiroshi; Ohta, Hisashi

doi:10.1097/00001756-200106130-00048

Cited by 18 publications

(11 citation statements)

References 17 publications

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“…The less active enantiomer of J-113397, the (-)-enantiomer, presented much lower (at least 70-fold lower) affinity for ORL-1 [48,51]. (Table 1) [37,[48][49][50]. J-113397 at concentrations 1-10 μM did not have any effect in the basal level of [ 35 S]GTP S binding or cyclic AMP production [37,49,50,52].…”

Section: J-113397mentioning

confidence: 94%

“…This compound, prepared to protect N/OFQ(1-13)NH 2 from degradation by aminopeptidases, showed lower binding affinity for the ORL-1 receptor, and was unable to activate the receptor, being characterized as a selective ORL-1 antagonist in the GPI (pA 2 = 7.02) and MVD (pA 2 = 6.75) bioassays [35]. However, this ligand showed agonist activity in the [ 35 S]GTP S binding [36,37], the cyclic AMP formation in CHO cells transfected with the ORL-1 receptors [38,39] and several other assays [33].…”

Section: Peptide Antagonistsmentioning

confidence: 99%

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The ORL-1 Receptor System: Are There Opportunities for Antagonists in Pain Therapy?

Fioravanti

Vanderah²

2008

CTMC

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Following the cloning of the classical opioid receptors (mu, delta and kappa), the opioid receptor like-1 (ORL-1) was identified as a G-protein coupled receptor (GPCR) with 65% structure homology to the other members of the opioid family. Its endogenous ligand nociception/orphanin FQ (N/OFQ) was discovered shortly thereafter, becoming the subject of investigation in numerous studies. Since activation of the ORL-1 receptor by N/OFQ leads to G alpha(i)-coupling and signal transduction similar to that of opioid receptors, N/OFQ was thought to have a role in pain modulation, similar to that of the endogenous opioids. Surprisingly, studies characterizing N/OFQ's effects on pain transmission yielded conflicting results, attributing to N/OFQ both pronociceptive and antinociceptive actions, depending on doses and routes of administration as well as species and sex of the subjects. With the development of selective and potent ORL-1 antagonists, many scientists believed these contradicting actions would be elucidated. Here we review the recent literature reporting the use of novel ORL-1 antagonists, both peptide and non-peptide, in different models of pain and discuss their use as research tools or potential drug candidates.

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Section: J-113397mentioning

confidence: 94%

Section: Peptide Antagonistsmentioning

confidence: 99%

The ORL-1 Receptor System: Are There Opportunities for Antagonists in Pain Therapy?

Fioravanti

Vanderah²

2008

CTMC

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“…The selectivity of action of 1-113397 on ORL-l receptor was confirmed in ORL-1 receptor-deficient mice (IcHIKAWA et al 2001). Cholecystokinins (CCKs) are endogenous neuropeptides interacting with G protein-coupled central and peripheral CCK-receptors of which there are at present two subtypes known, i.e., CCK1 = CCKA, mainly situated in the gastrointestinal tract, and CCKz = CCKB, predominantly present in the brain.…”

Section: Ligands Of Peptide Receptorsmentioning

confidence: 97%

Enantioselectivity in Drug-Receptor Interactions

Soudijn¹,

Wijngaarden²,

IJzerman³

2003

Stereochemical Aspects of Drug Action and Disposition

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A. IntroductionG protein-coupled receptors (GPCRs) constitute one of the largest superfamilies of proteins in the human genome. It is estimated that there are at least 600 and probably over 1000 receptor species. The known ones are the target for approximately 60% of today's medicines for such diverse disease states as high blood pressure (,B-adrenoceptor and angiotensin receptor antagonists), asthma (,B-adrenoceptor agonists), and acid overproduction in the stomach (histamine H2 receptor antagonists). Each member shares structural and/or sequence motifs and operates by common transduction mechanisms to mediate the transmission of extracellular signals into biochemical or electrophysiological responses within a cell. The signalling species is a specific endogenous molecule (e.g., neurotransmitter or hormone) which binds to the receptor. This results in activation of receptor and intracellularly located G proteins and propagation of the signal to effector molecules such as adenylyl cyclase. This enzyme converts ATP into cyclic AMP, the classical "second" messenger.Many neurotransmitters and hormones are chiral compounds. Among them are proteins and peptides, such as FSH (follicle stimulating hormone) and the endorphins, respectively. They are composed of natural amino acids, which, except for glycine, are all chiral. The translation machinery for peptide and protein synthesis has evolved to utilize only one of the chiral forms of amino acids, the L-form. The reason for this is not clear. Amino acids themselves may also act as endogenous signalling molecules for GPCRs. Examples are GABA (r-aminobutyric acid) acting on GABAB receptors, and metabotropic glutamate receptors for which L-glutamate and L-aspartate serve as signalling molecules. Other small endogenous molecules may serve a similar purpose. Among them are the classical biogenic amines, such as (nor)adrenaline, histamine, and serotonin, and numerous other examples, such as leukotrienes, adenosine, and ATP. This group hosts both nonchiral and chiral substances. Dopamine, serotonin, acetylcholine and histamine do not have a chiral center in their structure, whereas others possess one (adrenaline and noradrenaline) or more (adenosine and ATP). w. SOUDIJN et at number of cloned ("orphan") receptors, the endogenous ligand is not known (yet). An important effort to keep track of the latest information on receptors is the G protein-coupled receptor database which is maintained on the Internet (www.gpcr.org!7tm/).The earliest evidence for stereoselective receptor recognition was reported by PIUTII (1886) who pointed out that D-asparagine has a sweet taste, while the natural L-isomer is insipid. Interestingly, PASTEUR (1886) ascribed this finding to the presence of an optically active substance in the nervous mechanism of taste. Given our current understanding of olfactory receptors as a special branch of the large superfamily of G protein-coupled receptors, PASTEUR'S statement was well ahead of its time. CUSHNY (1926) was the first to review and pay particular atte...

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“…(Sim et al, 1995;Traynor and Nahorski, 1995). [ 35 S]GTPγ S binding was performed as described previously (Ozaki et al, 2000;Ichikawa et al, 2001). Membranes were incubated in GTPγ S binding buffer (20 mM Hepes, 100 mM NaCl, 10 mM MgCl 2 , 1 mM EDTA and 5 μM GDP, pH7.4) containing 200 pM [ 35 S]GTPγ S, 1.5 mg WGA PVT SPA scintillation beads (GE healthcare) and N/OFQ between 0.1 nM and 1 μM at 25°C for 2.5 h. Membrane-bound radioactivity was counted by topcount-HTS (PerkinElmer).…”

Section: Construction Of Rhesus Monkey Nop Receptor Expressing Cellsmentioning

confidence: 99%

Cloning and characterization of the rhesus monkey nociceptin/orphanin FQ receptor

Koga¹,

Ichikawa²,

Nambu³

et al. 2009

Genes Genet. Syst.

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We succeeded in cloning the rhesus monkey nociceptin/orphanin FQ peptide (NOP) receptor. The nucleotide sequence and amino acid sequence of the rhesus monkey NOP receptor were 95.9% and 97.8%, respectively, identical to the human NOP receptor. There was no significant difference between the rhesus monkey NOP receptor and the human NOP receptor in the binding affinity of 35 S]GTPγ S binding activated by N/OFQ using the membrane of the rhesus monkey NOP receptor. The antagonistic activity of (+)-J-113397 to the rhesus monkey NOP receptor was comparable to that to the human NOP receptor. Thus, N/OFQ acts via activation of the NOP receptor in both human and rhesus monkeys without significant species differences.

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

Cited by 18 publications

References 17 publications

The ORL-1 Receptor System: Are There Opportunities for Antagonists in Pain Therapy?

The ORL-1 Receptor System: Are There Opportunities for Antagonists in Pain Therapy?

Enantioselectivity in Drug-Receptor Interactions

Cloning and characterization of the rhesus monkey nociceptin/orphanin FQ receptor

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