Vasodilatory effects of adenosine A2 receptor agonists CGS 21680 and CGS 22492 in human vasculature

Targeted deletion of adenosine A3 receptors augments adenosine-induced coronary flow in isolated mouse heart

“…Here, referring to our earlier report (19), after examining adenosine-induced coronary vascular responses in A 2A KO hearts and blocking A 2B receptors in A 2A KO hearts, only A 3 receptors remained as a possible candidate site for adenosine receptor agonists to modulate coronary vascular response in murine hearts. In the present study, the A 3 receptor agonist Cl-IB-MECA did not affect coronary flow even at 100 nM, but at higher concentrations it increased coronary flow both in WT and A 3 KO hearts (Fig.…”

“…These data indicate that the presence of adenosine A3 receptors may either inhibit or negatively modulate coronary flow mediated by other adenosine receptor subtypes. coronary vasodilation; knockout mice; A 2A receptor knockout mice ADENOSINE PRODUCES potent coronary vasodilation in different mammalian species including bovine, canine, porcine, rat, guinea pig, mouse, and humans (1,2,8,18,19,27,34). The cardiovascular effects of adenosine are mediated by activation of four known cell surface adenosine receptors (A 1 , A 2A , A 2B , and A 3 ); however, the relative contribution of each adenosine receptor subtype in modulating coronary flow is not yet fully understood (11,21,23,32).…”

Adenosine Receptors and the Heart: Role in Regulation of Coronary Blood Flow and Cardiac Electrophysiology

“…Most of what is known about adenosine-mediated coronary regulation is derived from pharmacologic studies using a broad spectrum of experimental models (Abebe et al 1994; Belardinelli et al 1998; Berne 1980; Deussen et al 2006; Flood et al 2002; Hasan et al 2000; Hori and Kitakaze 1991; Makujina et al 1992; Mustafa and Abebe 1996). Applying an ever-expanding collection of highly selective AR analogs (both agonists and antagonists) in such a variety of models has confirmed that the A 2A AR is the predominant subtype mediating adenosine-induced coronary vasodilation (Belardinelli et al 1998; Shryock et al 1998).…”

“…Applying an ever-expanding collection of highly selective AR analogs (both agonists and antagonists) in such a variety of models has confirmed that the A 2A AR is the predominant subtype mediating adenosine-induced coronary vasodilation (Belardinelli et al 1998; Shryock et al 1998). However, the pharmacologic approach is limited by the selectivity of the ligands and/or potency, and frequently results in only indirect evidence that activation of other AR subtypes modifies adenosine-mediated coronary responses (Kemp and Cocks 1999; Makujina et al 1992; Talukder et al 2002b). The adventage of gene-modified models with targeted deletion or overexpression of a single AR subtype has allowed a more complete evaluation of adenosine-mediated responses than previously possible through agonist/antagonist studies alone.…”

Effects of the new A2 adenosine receptor antagonist 8FB‐PTP, an 8 substituted pyrazolo‐triazolo‐pyrimidine, on in vitro functional models

“…Moreover, in functional tests the drug is equally potent on both Al and A2 receptors (Sabouni et al, 1990;Makujina et al, 1992 Ao1>" !conflicting data could be partially explained by possible species __________________________________ differences in receptor density or subtypes. In the light of this, -9 -8 -7 -6 -5 -4 -3 it is clear why CGS 15943 has not become a reference A2…”