Adenosine A₁ receptor is a member of the adenosine receptor group of G protein-coupled receptor. Specifically, the A₁ receptor is relevant to sleep promotion by inhibiting cholinergic neurons in the basal forebrain that promote arousal. Besides, the A₁ receptor also exists in the smooth muscle of the whole vascular system. Endogenous adenosine A₁ and A_2A receptors are thought to play a role in regulating myocardial oxygen consumption and coronary blood flow. Moreover, stimulating the A₁ receptor reduces the conduction of electrical pulse and inhibiting the function of pacemaker cells. So, it can inhibit the heart rate and decrease the heart rate. This makes adenosine a useful drug for the treatment and diagnosis of tachyarrhythmia or tachyarrhythmia.

Furthermore, A₁AR activation can cause mechanisms involving G_i, PKC, and extracellular signal-regulated kinase (ERK) activation. And this results in preventing renal IR injury in vivo and in vitro models. Here, we will introduce a potent and selective irreversible A₁ adenosine receptor (A₁AR) antagonist, FSCPX.

FSCPX is a Selective Irreversible Antagonist of A₁AR.

First of all, FSCPX is a selective irreversible antagonist of A₁AR, with low nanomolar potency for binding to the A₁AR. Meanwhile, FSCPX modifies the effect of NBTI by reducing the interstitial adenosine level in the guinea pig atrium. NBTI is a nucleoside transport inhibitor.

In the second place, FSCPX irreversibly blocks the binding of [³H]DPCPX, with an IC₅₀ of 11.8 nM in DDT₁ MF2 cells. Nonetheless, FSCPX with 20 μM for 48 h prevents the increased resistance against necrosis and apoptosis in A₁AR-overexpressing LLC-PK1 cells. Particularly, FSCPX reverses the upregulation of HSP27 mRNA and protein in A₁AR-overexpressing LLC-PK1 cells. Interestingly, FSCPX has no effect on the mRNA or protein for HSP70.

All in all, FSCPX is a Selective Irreversible Antagonist of A₁AR.

References:

H T Lee, et al. Kidney Int. 2007 Jun;71(12):1249-61.