The in vitro pharmacological profile of KR31080, a nonpeptide AT1receptor antagonist
| Autor: | Sunkyung Lee, S.-E. Yoo, Ki Whan Hong, Chi Dae Kim |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
medicine.medical_specialty
Pyridines Tetrazoles Aorta Thoracic In Vitro Techniques 1-Sarcosine-8-Isoleucine Angiotensin II Receptor Angiotensin Type 2 Losartan Muscle Smooth Vascular Receptor Angiotensin Type 1 Iodine Radioisotopes Angiotensin Receptor Antagonists Cerebellum Internal medicine Renin–angiotensin system medicine Animals Humans Pharmacology (medical) Receptor Pharmacology Membranes Angiotensin II receptor type 1 Chemistry Angiotensin II Ligand binding assay Imidazoles Antagonist Recombinant Proteins Endocrinology Cattle Rabbits Antagonism Muscle Contraction medicine.drug |
| Zdroj: | Fundamental & Clinical Pharmacology. 12:64-69 |
| ISSN: | 1472-8206 0767-3981 |
| DOI: | 10.1111/j.1472-8206.1998.tb00925.x |
| Popis: | KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[2'-(1H-tetrazol-5-yl] biphenyl-4-yl(methyl(-3H-imidazo(4,5-b(pyridine) is a potent inhibitor of angiotensin type 1 (AT 1 ) receptors in rabbit aorta and human recombinant AT 1 receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (AII) with decreased maximal response (pD' 2 =10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific ( 125 I]AII binding to rabbit aortic membranes (AT 1 receptors) and [ 125 I][Sar 1 , Ile 8 ]AII binding to human recombinant AT 1 receptors in a concentration-dependent manner with IC 50 values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [ 125 I]AII binding to bovine cerebellum membranes (AT 2 receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT 1 receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT 1 selective angiotensin receptor antagonist which exerts a competitive antagonism in the [ 125 I]AII binding assay and insurmountable AT 1 receptor antagonism in the functional study. |
| Databáze: | OpenAIRE |
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