Allosteric interactions within the AT1 angiotensin receptor homodimer: Role of the conserved DRY motif

2012 ◽  
Vol 84 (4) ◽  
pp. 477-485 ◽  
Author(s):  
Bence Szalai ◽  
László Barkai ◽  
Gábor Turu ◽  
László Szidonya ◽  
Péter Várnai ◽  
...  
Keyword(s):  
Angiotensin Receptor ◽  
Allosteric Interactions ◽  
Dry Motif

scholarly journals Transactivation within the AT1 angiotensin receptor homodimer: the role of the conserved DRY motif

2009 ◽  
Vol 9 (Suppl 2) ◽  
pp. A51
Author(s):  
Bence Szalai ◽  
Péter Várnai ◽  
László Hunyady
Keyword(s):  
Angiotensin Receptor ◽  
Dry Motif

Drug Interactions with Angiotensin Receptor Blockers: Role of Human Cytochromes P450

2016 ◽  
Vol 17 (7) ◽  
pp. 681-691 ◽  
Author(s):  
Ruirui Yang ◽  
Zhiqiang Luo ◽  
Yang Liu ◽  
Mohan Sun ◽  
Ling Zheng ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Cytochromes P450 ◽  
Angiotensin Receptor Blockers ◽  
Angiotensin Receptor ◽  
Receptor Blockers

scholarly journals The Role of Apelin on the Alleviative Effect of Angiotensin Receptor Blocker in Unilateral Ureteral Obstruction-Induced Renal Fibrosis

Nephron Extra ◽  
2012 ◽  
Vol 2 (1) ◽  
pp. 39-47 ◽  
Author(s):  
Masashi Nishida ◽  
Yasuko Okumura ◽  
Tatsujiro Oka ◽  
Kentaro Toiyama ◽  
Seiichiro Ozawa ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Angiotensin Receptor Blocker ◽  
Unilateral Ureteral Obstruction ◽  
Receptor Blocker ◽  
Angiotensin Receptor

Heart Failure Therapy in 2016

2016 ◽  
Vol 51 (1) ◽  
pp. 79-82
Author(s):  
Douglas L. Jennings
Keyword(s):  
Heart Failure ◽  
Recent Literature ◽  
Residual Disease ◽  
Angiotensin Receptor ◽  
Heart Failure Therapy ◽  
Call To Action ◽  
Neprilysin Inhibitor ◽  
Drug Regimens ◽  
Contemporary Practice

Heart failure (HF) continues to afflict millions of Americans, resulting in substantial clinical and economic burden to our society. Recent literature has highlighted the role of 2 novel therapies (an angiotensin receptor blocker/neprilysin inhibitor and ivabradine) in further reducing residual disease in HF. Simultaneously, evidence has mounted suggesting that older therapies like digoxin are not effective in contemporary practice and, in fact, may be harmful. This editorial summarizes the most recently published articles pertaining to both new and old HF therapies and provides a call to action to pharmacists on how to shift patients toward effective drug regimens.

scholarly journals Mutations in the ‘DRY’ motif of the CB1 cannabinoid receptor result in biased receptor variants

2014 ◽  
Vol 54 (1) ◽  
pp. 75-89 ◽  
Author(s):  
Pál Gyombolai ◽  
András D Tóth ◽  
Dániel Tímár ◽  
Gábor Turu ◽  
László Hunyady
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Double Mutant ◽  
Cannabinoid Receptor ◽  
Camp Accumulation ◽  
Protein Activation ◽  
Cb1 Cannabinoid Receptor ◽  
G Protein Activation ◽  
Dry Motif

The role of the highly conserved ‘DRY’ motif in the signaling of the CB1cannabinoid receptor (CB1R) was investigated by inducing single-, double-, and triple-alanine mutations into this site of the receptor. We found that the CB1R-R3.50A mutant displays a partial decrease in its ability to activate heterotrimeric Goproteins (∼80% of WT CB1R (CB1R-WT)). Moreover, this mutant showed an enhanced basal β-arrestin2 (β-arr2) recruitment. More strikingly, the double-mutant CB1R-D3.49A/R3.50A was biased toward β-arrs, as it gained a robustly increased β-arr1 and β-arr2 recruitment ability compared with the WT receptor, while its G-protein activation was decreased. In contrast, the double-mutant CB1R-R3.50A/Y3.51A proved to be G-protein-biased, as it was practically unable to recruit β-arrs in response to agonist stimulus, while still activating G-proteins, although at a reduced level (∼70% of CB1R-WT). Agonist-induced ERK1/2 activation of the CB1R mutants showed a good correlation with their β-arr recruitment ability but not with their G-protein activation or inhibition of cAMP accumulation. Our results suggest that G-protein activation and β-arr binding of the CB1R are mediated by distinct receptor conformations, and the conserved ‘DRY’ motif plays different roles in the stabilization of these conformations, thus mediating both G-protein- and β-arr-mediated functions of CB1R.

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