Targeting G protein-coupled receptors for heart failure treatment.

Heart failure remains a leading cause of morbidity and mortality worldwide. Current treatment for patients with heart failure include drugs targeting G protein-coupled receptors such as β-adrenoceptor antagonists (β-blockers) and angiotensin II type 1 receptor antagonists (or angiotensin II receptor blockers). However, many patients progress to advanced heart failure with persistent symptoms, despite treatment with available therapeutics that have been shown to reduce mortality and mortality.

Examining the Role of the Linker in Bitopic -Substituted Adenosine Derivatives Acting as Biased Adenosine A Receptor Agonists.

The adenosine A receptor is a therapeutic target based on its ability to provide cardioprotection during episodes of myocardial ischemia and reperfusion injury. However, the clinical translation of AR agonists has been hindered by dose-limiting adverse effects (bradycardia and hypotension). Previously, we demonstrated that the bitopic agonist VCP746 (), consisting of an adenosine pharmacophore linked to an allosteric moiety, can stimulate cardioprotective AR signaling effects in the absence of unwanted bradycardia.

α-Adrenoceptors activate mTOR signalling and glucose uptake in cardiomyocytes.

The capacity of G protein-coupled receptors to modulate mechanistic target of rapamycin (mTOR) activity is a newly emerging paradigm with the potential to link cell surface receptors with cell survival. Cardiomyocyte viability is linked to signalling pathways involving Akt and mTOR, as well as increased glucose uptake and utilization. Our aim was to determine whether the α-adrenoceptor (AR) couples to these protective pathways, and increased glucose uptake.