Cardiac effects of adenosine in A(2A) receptor knockout hearts: uncovering A(2B) receptors.
To clarify the relative roles of A(2) adenosine receptor subtypes in the regulation of coronary flow and myocardial contractility, coronary vascular and functional responses to adenosine and its analogs were examined in isolated wild-type (WT) and A(2A) receptor knockout (A(2A)KO) mouse hearts. Nonselective agonists adenosine and 5'-N-ethyl-carboxamido-adenosine (NECA) increased coronary flow in A(2A)KO hearts, albeit with a rightward shift of concentration-response curves and decreased maximal vasodilation compared with WT hearts. 2-p-(2-Carboxy-ethyl)phenethylamino-5'-N-ethyl-carboxamidoadenosine (CGS-21680, a selective A(2A) receptor agonist) increased coronary flow in WT hearts but did not affect A(2A)KO hearts. Adenosine and NECA each elicited equal maximal increases in developed pressure in WT and A(2A)KO hearts, whereas CGS-21680 did not affect developed pressure in A(2A)KO hearts. Alloxazine, a selective A(2B) receptor antagonist, attenuated NECA-induced coronary vasodilation (from 202 +/- 14% to 128 +/- 9% of baseline, P < 0.05) and NECA-induced increases in developed pressure (from 133 +/- 8% to 112 +/- 7% of baseline, P < 0.05) in A(2A)KO hearts. Together, these findings support the conclusion that A(2B) adenosine receptor activation increases coronary flow and developed pressure in isolated murine hearts.
Morrison
R Ray
RR
Department of Pediatrics, The Brody School of Medicine at East Carolina University, Greenville, North Carolina 27858, USA.
Talukder
M A Hassan
MA
Ledent
Catherine
C
Mustafa
S Jamal
SJ
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D005415:Flavins / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D010627:Phenethylamines / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D018047:Receptors, Purinergic P1 / Q000235:genetics* / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology; D017725:Ventricular Pressure / Q000187:drug effects / Q000502:physiology
D000959:Antihypertensive Agents; D005415:Flavins; D010627:Phenethylamines; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); C008173:isoalloxazine; D000241:Adenosine