Biomaterial Database

Species differences in the binding characteristics of [125I]IRL-1620, a potent agonist specific for endothelin-B receptors. 1994

P Nambi, and M Pullen, and W Spielman

SmithKline Beecham Pharmaceuticals, Department of Renal Pharmacology, King of Prussia, Pennsylvania.

[125I]Tyr13-Suc-[Glu9,Ala11,15]-Endothelin-1 (8-21) ([125I]IRL-1620) displayed specific, saturable and high affinity binding to membranes prepared from rat and dog cerebellum, rat and human lung and cloned human endothelin-B (ETB) receptors. The apparent dissociation constant (Kd) for rat cerebellum, dog cerebellum, rat lung, human lung and human ETB clone were 69.1, 34.8, 128, 71.9, and 115 pM, respectively. The maximum binding (Bmax) to these membranes were 3.2, 0.71, 1.67, 1.85 and 62.3 pmol/mg of protein for rat cerebellum, dog cerebellum, rat lung, human lung and human ETB clone, respectively. Unlabeled endothelin-1 (ET-1), ET-3 and sarafotoxin 6c (S6c) displaced [125I]IRL-1620 binding to these membranes with similar affinity (IC50 = 0.1-2.5 nM), whereas cyclo(D-Trp,D-Asp,L-Pro,D-Val,L-Leu), a selective antagonist for ETA receptors, had no effect on [125I]IRL-1620 binding up to 1 microM. Time course experiments of association and dissociation indicated that [125]IRL-1620 binding to dog and human tissues and human ETB clone was rapid and reversible, whereas in rat tissues, the binding was rapid but irreversible, suggesting that this might be due to species difference. [125I]ET-1 binding was irreversible in all the tissues tested. No binding of [125I]IRL-1620 was detectable in rat vascular smooth muscle cells or cloned human ETA receptors. These data indicate that [125I]IRL-1620 is highly selective for ETB receptors and the reversible binding characteristics of this ligand appears to be species-dependent.

UI	MeSH Term	Description	Entries
D008168	Lung	Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.	Lungs
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010446	Peptide Fragments	Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.	Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D002531	Cerebellum	The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.	Cerebella,Corpus Cerebelli,Parencephalon,Cerebellums,Parencephalons
D004285	Dogs	The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)	Canis familiaris,Dog
D006224	Cricetinae	A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.	Cricetus,Hamsters,Hamster
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining