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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1998-9-2
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pubmed:abstractText |
G protein activation by the agonist-occupied nociceptin- (orphanin FQ-) receptor in rat cerebral cortex was studied by characterizing the nociceptin-stimulated binding of the radiolabeled guanylyl triphosphate (GTP) analog 35S-guanylyl-5'-O-(gamma-thio)-triphosphate (GTPgammaS). Using 3H-Tyr14- and 125I-Tyr14-nociceptin in saturation and displacement receptor binding studies, a single high-affinity (Kd 21.6-116.7 pM) and high-capacity binding site for nociceptin (orphanin FQ) in membranes and sections of rat cerebral cortex was identified. Stable GTP analogs and NaCl lowered the affinity only moderately by 2- to 3-fold, but under these conditions nociceptin stimulated the binding of 35S-GTPgammaS to G proteins in the membranes with a potency about 100-fold lower (EC50 9.11 nM). It was estimated that this stimulation was due to a 29-fold increase in the affinity from Kd 45. 8 to 1.57 nM of only about 6.5% of the basal binding sites for GTPgammaS, and that at least 10 G protein binding sites could be stimulated by one receptor site. The link of this nociceptin-stimulated binding of GTP to the nociceptin receptor was further evidenced by the specificity of stimulation, as seen with nociceptin, nociceptin(1-13), D-Ala7-nociceptin and nociceptin(1-9), which paralleled that of their receptor affinities. Furthermore, the distribution in rat brain regions of the binding of 35S-GTPgammaS stimulated by nociceptin differed from that stimulated by the mu opioid agonist [D-Ala2, N-Me-Phe4, Gly5-ol)]-enkephalin. Especially, no stimulation by nociceptin was observed in caudate putamen, where also the absence of ORL1 receptors had been reported. The putative coupling of the high-affinity nociceptin receptor to the low-potency stimulation of GTPgammaS binding in rat cerebral cortex might be explained by the switch of a low part of occupied nociceptin binding sites to a very low-affinity state being stabilized at high peptide concentrations and catalytically stimulating the GTP binding.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Analgesics, Opioid,
http://linkedlifedata.com/resource/pubmed/chemical/Buffers,
http://linkedlifedata.com/resource/pubmed/chemical/Enkephalin, Ala(2)-MePhe(4)-Gly(5)-,
http://linkedlifedata.com/resource/pubmed/chemical/Enkephalins,
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine 5'-O-(3-Thiotriphosphate),
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Opioid Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Opioid,
http://linkedlifedata.com/resource/pubmed/chemical/nociceptin,
http://linkedlifedata.com/resource/pubmed/chemical/nociceptin receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-3565
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
286
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
896-902
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9694948-Analgesics, Opioid,
pubmed-meshheading:9694948-Animals,
pubmed-meshheading:9694948-Brain Chemistry,
pubmed-meshheading:9694948-Buffers,
pubmed-meshheading:9694948-Cerebral Cortex,
pubmed-meshheading:9694948-Enkephalin, Ala(2)-MePhe(4)-Gly(5)-,
pubmed-meshheading:9694948-Enkephalins,
pubmed-meshheading:9694948-Guanosine 5'-O-(3-Thiotriphosphate),
pubmed-meshheading:9694948-Guanosine Triphosphate,
pubmed-meshheading:9694948-Male,
pubmed-meshheading:9694948-Membranes,
pubmed-meshheading:9694948-Opioid Peptides,
pubmed-meshheading:9694948-Protein Binding,
pubmed-meshheading:9694948-Rats,
pubmed-meshheading:9694948-Rats, Wistar,
pubmed-meshheading:9694948-Receptors, Opioid,
pubmed-meshheading:9694948-Spinal Cord
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pubmed:year |
1998
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pubmed:articleTitle |
Nociceptin (orphanin FQ): high-affinity and high-capacity binding site coupled to low-potency stimulation of guanylyl-5'-O-(gamma-thio)-triphosphate binding in rat brain membranes.
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pubmed:affiliation |
Department of Peptide Pharmacology, Research Institute of Molecular Pharmacology, Berlin, Germany.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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