title: Role of A(2A)-adenosine receptor activation for ATP-mediated coronary vasodilation in guinea-pig isolated heart.
abstract: 1. Adenosine-5'-triphosphate (ATP) and adenosine are potent coronary vasodilators. ATP is rapidly converted to adenosine by ectonucleotidases. We examined whether coronary vasodilation caused by exogenous ATP is mediated by P(2) receptor activation or by A(2A)-adenosine receptor activation. 2. Effects of interventions on coronary conductance were determined by measuring coronary perfusion pressure in guinea-pig isolated hearts perfused at a constant flow of 10 ml min(-1). 3. ATP and adenosine both caused sustained, concentration-dependent increases of coronary conductance. Maximal responses to both agonists were equivalent. The values of pD(2) (+/-s.e.mean) for ATP and adenosine were 6.68+/-0.04 and 7.06+/-0.05, respectively. Adenosine was significantly more potent than ATP (P<0. 0001, n=10). 4. The values of pIC(50) for the selective A(2A)-adenosine receptor antagonist SCH58261 to antagonize equivalent responses to ATP and adenosine were 8.28+/-0.08 and 8.28+/-0.06 (P=0.99, n=6), respectively. 5. The non-selective adenosine receptor antagonists xanthine amine congener (XAC) and CGS15943 antagonized similarly the equivalent vasodilations caused by ATP (pIC(50) values 7.48+/-0.04 and 7.45+/-0.06, respectively) and adenosine (pIC(50) values 7. 37+/-0.13 and 7.56+/-0.11). 6. In contrast to ATP and adenosine, the two P(2) agonists 2-methylthio-ATP and uridine-5'-triphosphate failed to cause stable increases of coronary conductance, caused desensitization of vasodilator responses, and were not antagonized by SCH 58261, 8-parasulphophenyltheophylline, or XAC. 7. Glibenclamide attenuated coronary vasodilations caused by ATP and adenosine by 88 and 89%, respectively, but failed to attenuate those caused by 2-methylthio-ATP. 8. These results strongly suggest that sustained, submaximal coronary vasodilation caused by exogenous ATP is entirely mediated by adenosine acting upon A(2A)-adenosine receptors.
authors.affiliation: Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA.
authors.forename: K S
authors.initials: KS
authors.lastname: Erga
authors.forename: C N
authors.initials: CN
authors.lastname: Seubert
authors.forename: H X
authors.initials: HX
authors.lastname: Liang
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.forename: J C
authors.initials: JC
authors.lastname: Shryock
authors.forename: L
authors.initials: L
authors.lastname: Belardinelli
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010477:Perfusion; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: C092431:6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP; D018047:Receptors, Purinergic P1; D013873:Thionucleotides; C523965:alpha,beta-methyleneadenosine 5'-diphosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000243:Adenosine Deaminase; D000241:Adenosine; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester; C008501:2-methylthio-ATP