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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1995-4-12
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pubmed:abstractText |
A novel linear peptide fragment of endothelin-1 (ET-1), N-acetyl-[Ala11,15]ET-1[6-21] (BQ3020) has been identified as a potent and ETB-selective agonist. The present studies were conducted in order to characterize the binding of [125I]BQ3020 to the ETB receptor in rat cerebellum. [125I]BQ3020 (0.1 nM) bound with high specificity (90% of total binding) and selectivity for the ETB receptor. ET-1, ET-2, and ET-3 inhibited 0.1 nM [125I]BQ3020 binding with equivalent affinity (Ki values = 55-110 pM). The sarafotoxins S6a, S6b, and S6c also potently inhibited [125I]BQ3020 binding (Ki values = 55-2000 pM). The ETA-selective antagonist, BQ123 (100 microM) did not significantly inhibit [125I]BQ3020 binding. Ligand saturation studies indicated that [125I]BQ3020 labeled a single class of recognition sites with very high affinity (Kd = 31 pM) and limited capacity (Bmax = 570 fmol/mg protein). High affinity 0.1 nM [125I]BQ3020 binding was reduced by 40-50% in the presence of 1 mM guanine nucleotides. Additional competition studies indicated that ET-1 and ET-2 produced biphasic inhibition curves in competing for 0.5 nM [125I]BQ3020. The high affinity component of the ET-1 inhibition curve was subsequently eliminated in the presence of 1 mM GTP-gamma-S The guanine nucleotide sensitivity of [125I]BQ3020 binding offers the possibility that different functional consequences of ETB receptor activation may be mediated by multiple affinity states of the receptor. The present data demonstrate that [125I]BQ3020 is a potent and selective agonist for the ETB receptor that can discriminate high and low affinity states of the ETB receptor.
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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/BQ 3020,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelins,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Iodine Radioisotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Endothelin
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0006-8993
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
28
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pubmed:volume |
665
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
33-8
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pubmed:dateRevised |
2003-11-14
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pubmed:meshHeading |
pubmed-meshheading:7882015-Animals,
pubmed-meshheading:7882015-Cerebellum,
pubmed-meshheading:7882015-Endothelins,
pubmed-meshheading:7882015-GTP-Binding Proteins,
pubmed-meshheading:7882015-Iodine Radioisotopes,
pubmed-meshheading:7882015-Peptide Fragments,
pubmed-meshheading:7882015-Radioligand Assay,
pubmed-meshheading:7882015-Rats,
pubmed-meshheading:7882015-Receptors, Endothelin
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pubmed:year |
1994
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pubmed:articleTitle |
Pharmacological characterization of the rat cerebellar endothelin B (ETB) receptor using the novel agonist radioligand [125I]BQ3020.
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pubmed:affiliation |
Rhône-Poulenc Rorer Central Research, Collegeville, PA 19426-0107.
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pubmed:publicationType |
Journal Article
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