Targeted deletion of adenosine A(3) receptors augments adenosine-induced coronary flow in isolated mouse heart.
To determine whether adenosine A(3) receptors participate in adenosine-induced changes in coronary flow, isolated hearts from wild-type (WT) and A(3) receptor knockout (A(3)KO) mice were perfused under constant pressure and effects of nonselective and selective agonists were examined. Adenosine and the selective A(2A) agonist 2-[p-(2-carboxyethyl)]phenylethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680) produced augmented maximal coronary vasodilation in A(3)KO hearts compared with WT hearts. Selective activation of A(3) receptors with 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA) at nanomolar concentrations did not effect coronary flow, but at higher concentrations it produced coronary vasodilation both in WT and A(3)KO hearts. Cl-IB-MECA-induced increases in coronary flow were susceptible to both pharmacological blockade and genetic deletion of A(2A) receptors. Because deletion or blockade of adenosine A(3) receptors augmented coronary flow induced by nonselective adenosine and the selective A(2A) receptor agonist CGS-21680, we speculate that this is due to removal of an inhibitory influence associated with the A(3) receptor subtype. These data indicate that the presence of adenosine A(3) receptors may either inhibit or negatively modulate coronary flow mediated by other adenosine receptor subtypes.
Talukder
M A Hassan
MA
Department of Pharmacology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27858, USA.
Morrison
R Ray
RR
Jacobson
Marlene A
MA
Jacobson
Kenneth A
KA
Ledent
Catherine
C
Mustafa
S Jamal
SJ
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects; D017353:Gene Deletion; D006339:Heart Rate; D051379:Mice; D018345:Mice, Knockout; D010627:Phenethylamines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D014230:Triazoles / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D017725:Ventricular Pressure
C110041:9-chloro-2-(2-furyl)-5-phenylacetylamino(1,2,4)triazolo(1,5-c)quinazoline; D010627:Phenethylamines; D011799:Quinazolines; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; D014230:Triazoles; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000241:Adenosine; C090034:2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide