Lys(199) mutation of the human angiotensin type 1 receptor differentially affects the binding of surmountable and insurmountable non-peptide antagonists

Journal of the Renin-angiotensin-aldosterone System : JRAAS
F L FierensG Vauquelin

Abstract

Many slow dissociating (insurmountable) non-peptide angiotensin type 1 receptor (AT1) antagonists contain,besides the acidic biphenyltetrazole substructure of losartan, a second acidic group to stabilise antagonist-receptor complexes. To investigate the involved basic amino-acids of the human AT1-receptor, wild-type and mutant receptors were transiently transfected in CHO-K1 cells and characterised by [3H]candesartan binding. Lys199-->Gln substitution decreased the affinity 45-fold for candesartan (95% insurmountable),18-fold for EXP3174 (70% insurmountable), 10-fold for irbesartan (40% insurmountable) and 5-fold for losartan (surmountable). His256 -->Ala substitution had only minor effects. This suggests that Lys199 is important for the tight binding of non-peptide antagonists.

References

Dec 1, 1995·The Journal of Biological Chemistry·K NodaS S Karnik
Jan 1, 1995·Journal of Cardiovascular Pharmacology·S MochizukiA Tomiyama
Mar 1, 1995·Journal of Cardiovascular Pharmacology·A R RenzettiA Giachetti
Jun 9, 1995·The Journal of Biological Chemistry·Y YamanoT Hamakubo
Jul 19, 1994·Proceedings of the National Academy of Sciences of the United States of America·H T SchambyeT W Schwartz
Aug 1, 1997·Biological & Pharmaceutical Bulletin·K TamuraK Hashimoto
Mar 6, 1999·The Journal of Biological Chemistry·S MiuraS S Karnik
Jul 8, 1999·European Journal of Pharmacology·F L FierensG Vauquelin

❮ Previous
Next ❯

Citations

Aug 27, 2011·Journal of Chemical Information and Modeling·Marijn P A SandersJan P G Klomp
Oct 5, 2013·Journal of Chemical Information and Modeling·Minos-Timotheos MatsoukasTheodore Tselios
Oct 13, 2005·Journal of Cardiovascular Pharmacology·David E MireMichael K Pugsley
Apr 8, 2006·Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension·Georges VauquelinIsabelle Van Liefde
Aug 10, 2011·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Yoshihiro KiyaKeijiro Saku
May 31, 2002·Drugs·Marc De Gasparo
Jul 12, 2014·Journal of Molecular Endocrinology·Pitchai Balakumar, Gowraganahalli Jagadeesh
Jul 16, 2008·Molecular and Cellular Endocrinology·I Van Liefde, G Vauquelin
Jan 22, 2005·Fundamental & Clinical Pharmacology·G Vauquelin, I Van Liefde
Nov 3, 2004·Trends in Endocrinology and Metabolism : TEM·László Hunyady, Gábor Turu
Mar 26, 2004·Biochemical Pharmacology·Ilse VerheijenGeorges Vauquelin
Jan 26, 2016·British Journal of Pharmacology·Georges VauquelinDavid C Swinney
Apr 16, 2003·Biochemical Pharmacology·Minh Tam LeGeorges Vauquelin
Feb 7, 2003·Fundamental & Clinical Pharmacology·G VauquelinP M L Vanderheyden
Jun 27, 2017·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Takanobu TakezakoKoichi Node
Mar 1, 2001·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Georges VauquelinPatrick Ml Vanderheyden
Apr 13, 2007·Physiological Reviews·Laerte OliveiraAntonio C M Paiva
Dec 3, 2010·The Journal of Pharmacology and Experimental Therapeutics·Mami OjimaHideaki Nagaya

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.