Molecular Mechanism Underlying Inverse Agonist of Angiotensin II Type 1 Receptor
نویسندگان
چکیده
منابع مشابه
Molecular mechanism underlying inverse agonist of angiotensin II type 1 receptor.
To delineate the molecular mechanism underlying the inverse agonist activity of olmesartan, a potent angiotensin II type 1 (AT1) receptor antagonist, we performed binding affinity studies and an inositol phosphate production assay. Binding affinity of olmesartan and its related compounds to wild-type and mutant AT1 receptors demonstrated that interactions between olmesartan and Tyr113, Lys199, ...
متن کاملSmall Molecules with Similar Structures Exhibit Agonist, Neutral Antagonist or Inverse Agonist Activity toward Angiotensin II Type 1 Receptor
Small differences in the chemical structures of ligands can be responsible for agonism, neutral antagonism or inverse agonism toward a G-protein-coupled receptor (GPCR). Although each ligand may stabilize the receptor conformation in a different way, little is known about the precise conformational differences. We synthesized the angiotensin II type 1 receptor blocker (ARB) olmesartan, R239470 ...
متن کاملStructure-Function Basis of Attenuated Inverse Agonism of Angiotensin II Type 1 Receptor Blockers for Active-State Angiotensin II Type 1 Receptor s
Ligand-independent signaling by the angiotensin II type 1 receptor (AT1R) can be activated in clinical settings by mechanical stretch and autoantibodies as well as receptor mutations. Transition of the AT1R to the activated state is known to lower inverse agonistic efficacy of clinically used AT1R blockers (ARBs). The structure-function basis for reduced efficacy of inverse agonists is a fundam...
متن کاملStructure-Function Basis of Attenuated Inverse Agonism of Angiotensin II Type 1 Receptor Blockers for Active-State Angiotensin II Type 1 Receptor.
Ligand-independent signaling by the angiotensin II type 1 receptor (AT1R) can be activated in clinical settings by mechanical stretch and autoantibodies as well as receptor mutations. Transition of the AT1R to the activated state is known to lower inverse agonistic efficacy of clinically used AT1R blockers (ARBs). The structure-function basis for reduced efficacy of inverse agonists is a fundam...
متن کاملAngiotensin II type 1 receptor blockers.
In the 1970s, a series of observations demonstrated that angiotensin II has deleterious effects on the heart and kidney and that patients with high levels of plasma renin activity are at a higher risk of developing stroke or myocardial infarction than those with low plasma renin activity.1,2 Thereafter, the development of pharmacological probes that block the renin-angiotensin system helped def...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 2006
ISSN: 0021-9258
DOI: 10.1074/jbc.m602144200