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PMID: 16565729 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

S-nitrosylation of cysteine 289 of the AT1 receptor decreases its binding affinity for angiotensin II.

British journal of pharmacology ·Vol. 148 ·No. 3 ·2006-06-00 ·Pages 306-13

Leclerc PC, Lanctot PM, Auger-Messier M, Escher E, Leduc R, Guillemette G

Abstract

1. Nitric oxide (NO) is known to affect the properties of various proteins via the S-nitrosylation of cysteine residues. This study evaluated the direct effects of the NO donor sodium nitroprusside (SNP) on the pharmacological properties of the AT1 receptor for angiotensin II expressed in HEK-293 cells. 2. SNP dose-dependently decreased the binding affinity of the AT1 receptor without affecting its total binding capacity. This modulatory effect was reversed within 5 min of removing SNP. 3. The effect of SNP was not modified in the presence of the G protein uncoupling agent GTPgammaS or the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. 4. The binding properties of a mutant AT1 receptor in which all five cysteine residues within the transmembrane domains had been replaced by serine was not affected by SNP. Systematic analysis of mutant AT1 receptors revealed that cysteine 289 conferred the sensitivity to SNP. 5. These results suggest that NO decreased the binding affinity of the AT1 receptor by S-nitrosylation of cysteine 289. This modulatory mechanism may be particularly relevant in pathophysiological situations where the beneficial effects of NO oppose the deleterious effects of angiotensin II.

MeSH Terms
Amino Acid Substitution Angiotensin II/metabolism Cysteine/metabolism Dose-Response Relationship, Drug Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology Guanylate Cyclase/antagonists & inhibitors Humans Nitric Oxide Donors/metabolism,pharmacology Nitroprusside/pharmacology Protein Binding/drug effects Receptor, Angiotensin, Type 1/drug effects,genetics,metabolism
Chemicals
Nitric Oxide Donors Receptor, Angiotensin, Type 1 Angiotensin II Nitroprusside Guanosine 5'-O-(3-Thiotriphosphate) Guanylate Cyclase Cysteine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Leclerc Patrice C
Department of Pharmacology, Faculty of Medicine and Health Sciences, University of Sherbrooke, 3001-12th Avenue North, Sherbrooke, Quebec, Canada J1H 5N4.
Lanctot Pascal M
Auger-Messier Mannix
Escher Emanuel
Leduc Richard
Guillemette Gaetan
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Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
Published
2006-06-00
Pages
306-13
Language
English
Region
England
NLM ID
7502536
PMCID
PMC1751562
Subset
IM
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