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S ‐nitrosylation of cysteine 289 of the AT 1 receptor decreases its binding affinity for angiotensin II
Author(s) -
Leclerc Patrice C,
Lanctot Pascal M,
AugerMessier Mannix,
Escher Emanuel,
Leduc Richard,
Guillemette Gaetan
Publication year - 2006
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706725
Subject(s) - cysteine , receptor , chemistry , angiotensin ii , s nitrosylation , sodium nitroprusside , nitrosylation , mutant , nitric oxide , transmembrane protein , biochemistry , pharmacology , biology , enzyme , gene , organic chemistry
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 AT 1 receptor for angiotensin II expressed in HEK‐293 cells. 2 SNP dose‐dependently decreased the binding affinity of the AT 1 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 GTP γ S or the soluble guanylyl cyclase inhibitor 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one. 4 The binding properties of a mutant AT 1 receptor in which all five cysteine residues within the transmembrane domains had been replaced by serine was not affected by SNP.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 AT 1 receptors revealed that cysteine 289 conferred the sensitivity to SNP. 5 These results suggest that NO decreased the binding affinity of the AT 1 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.British Journal of Pharmacology (2006) 148 , 306–313. doi: 10.1038/sj.bjp.0706725