Contribution of adenosine to isoproterenol-stimulated prostacyclin production in rabbit heart.
This study investigated adenosine's contribution to isoproterenol-stimulated prostacyclin production, measured as 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) output, and mechanical function in the isolated rabbit heart perfused with Krebs-Henseleit buffer. The isoproterenol-induced increase in 6-keto-PGF1 alpha was diminished by adenosine (10 microM), the A1 receptor antagonist 1,3-dipropyl, 8-cyclopentylxanthine (DPCPX 0.06 microM), and the A2 receptor agonist CGS-21680 (0.6 microM); CGS-21680 did not decrease heart rate (HR) or myocardial contractility (dP/dt(max)). The isoproterenol-induced increase in 6-keto-PGF1 alpha was potentiated by the A1 receptor agonist 1-deaza,2-chloro,N6-cyclopentyladenosine (DCCA, 0.6 microM) and the A2 receptor antagonist 3,7-dimethyl,1-propargylxanthine (DMPX, 6 microM). The isoproterenol-induced increase in dP/dt(max) and HR was diminished by adenosine, DCCA, and DMPX. DPCPX enhanced dP/dt(max) and HR and prevented the decrease by adenosine and DCCA of the isoproterenol-induced increase in HR and dP/dt(max); the increase by DCCA but not the decrease by adenosine in 6-keto-PGF1 alpha output was abolished. DMPX abolished the effect of adenosine and CGS-21680 to reduce isoproterenol-stimulated 6-keto-PGF1 alpha. These data suggest that adenosine generated in response to isoproterenol attenuates its effect on HR and dP/dt(max) through A1 receptors and on prostacyclin synthesis via A2 receptors.
Cano
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Department of Pharmacology, School of Medicine, University of Tennessee, Memphis 38163.
Qureshi
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Carter
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Malik
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KU
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000241:Adenosine / Q000502:physiology*; D000818:Animals; D011464:Epoprostenol / Q000096:biosynthesis*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D011983:Receptors, Purinergic / Q000502:physiology
D011983:Receptors, Purinergic; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D000241:Adenosine; D007545:Isoproterenol