| Radioligand binding characterization of the bradykinin B(2) receptor in the rabbit and pig ileal smooth muscle. | |
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MedLine Citation:
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PMID: 20307535 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Several species-related differences have been reported in kinin B(2) receptor pharmacology. The present study aimed to evaluate the affinity of the bradykinin B(2) receptor antagonist MEN16132 for the rabbit and pig B(2) receptor, and radioligand binding experiments using [(3)H]bradykinin and membranes of rabbit and pig ileum smooth muscle were conducted. The [(3)H]bradykinin binding was characterized by homologous displacement curves indicating K(d) values of 0.65 and 0.33nM in rabbit and pig, respectively. The B(2) receptor specificity of [(3)H]bradykinin binding was shown by the low affinity (>microM) displayed by agonists ([desArg(9)]bradykinin and Lys[desArg(9)]bradykinin) and antagonists [Leu(8),desArg(9)]bradykinin and Lys[Leu(8),desArg(9)]bradykinin) selective for the B(1) receptor. The affinity of MEN16132 and other antagonists was determined by inhibition curves (pK(i) values in the rabbit and pig assay, respectively): MEN16132 (10.4 and 10.3) and peptide compounds such as icatibant (10.1 and 9.9) and MEN11270 (10.3 and 10.1) displayed subnanomolar potency in both assays; the nonpeptide LF16-0687 (8.4 and 8.5) and FR173657 (8.2 and 9.1) exhibited a different affinity pattern, whereas WIN64338 displayed low affinity (5.7 and <or=5). Results are discussed focusing on comparisons with previous findings obtained in rabbit and pig vascular functional assays, but also with those obtained in analog guinea pig and mouse assays and at the human B(2) receptor. An attempt to highlight differences which can undertake ligands selectivity across the species is presented. In conclusion, the present study indicates MEN16132 as the only nonpeptidic compound which displays an even subnanomolar affinity for the rabbit and pig B(2) receptor. |
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Authors:
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Stefania Meini; Paola Cucchi; Claudio Catalani; Francesca Bellucci; Paolo Santicioli; Sandro Giuliani; Carlo Alberto Maggi |
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Publication Detail:
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Type: Journal Article Date: 2010-03-20 |
Journal Detail:
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Title: European journal of pharmacology Volume: 635 ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-04-30 Completed Date: 2010-08-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 34-9 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Menarini Ricerche S.p.A., via Rismondo 12A, Florence, Italy. smeini@menarini-ricerche.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bradykinin / metabolism Cell Membrane / metabolism Female Guinea Pigs Humans Ileum* Ligands Male Mice Muscle, Smooth / cytology, metabolism* Ornithine / analogs & derivatives, metabolism, pharmacology Protein Binding / drug effects Rabbits Receptor, Bradykinin B2 / antagonists & inhibitors, metabolism* Substrate Specificity Sulfonamides / metabolism, pharmacology Swine* |
| Chemical | |
Reg. No./Substance:
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0/(4-amino-5-(4-(4-(2,4-dichloro-3-(2,4-dimethyl-8-quinolyloxymethyl)phenylsulfonamido)tetrahydro-2H-4-pyranoylcarbonyl)piperazino)-5-oxopentyl)(trimethyl)ammonium; 0/Ligands; 0/Receptor, Bradykinin B2; 0/Sulfonamides; 58-82-2/Bradykinin; 7006-33-9/Ornithine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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