Differential antagonism by 1,3-dipropylxanthine-8-cyclopentylxanthine and 9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo(1,5-c)quinazolin-5-im ine of the effects of adenosine derivatives in the presence of isoprenaline on contractile response and cyclic AMP content in cardiomyocytes. Evidence for the coexistence of A1- and A2-adenosine receptors on cardiomyocytes.
The antagonism by the A1-adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and the A2-adenosine receptor antagonist [9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo (1,5-c)quinazolin-5-imine] (CGS 15943A) of the effects of the A1-adenosine receptor agonist (-)-N6-phenylisopropyladenosine (R-PIA) and the A2-adenosine receptor agonist 5'-N-ethyl-carboxamideadenosine (NECA) in the presence of isoprenaline on contractile response and cyclic AMP (cAMP) content in cardiomyocytes from guinea pig cardiac ventricles were studied. In electrically driven (1 Hz) guinea pig ventricular cardiomyocytes R-PIA concentration-dependently (0.0001-100 microM) reduced the stimulatory effects of isoprenaline (0.01 microM) on contractile response and on cAMP content. The A1-adenosine receptor antagonist DPCPX (0.3 microM) antagonized the effects of R-PIA on contractile reponse and on cAMP content, whereas the A2-adenosine receptor antagonist CGS 15943A (0.01 microM) was ineffective. NECA (0.0001-100 microM) reduced the effects of isoprenaline (0.01 microM) on contractile response to about the same extent as R-PIA. However, NECA did not change cAMP content. DPCPX (0.3 microM) antagonized the effects of NECA on contractile response and evoked a cAMP-increasing effect of NECA, which was 38% of the isoprenaline value at most. In contrast, CGS 15943A did not affect the reduction of contractile response induced by NECA, whereas CGS 15943A revealed a cAMP-decreasing effect of NECA (0.1-10 microM). This study provides functional evidence that both, cAMP-decreasing A1- and cAMP-increasing A2-adenosine receptors are present on ventricular cardiomyocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Behnke
N
N
Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Universität Hamburg, Federal Republic of Germany.
Müller
W
W
Neumann
J
J
Schmitz
W
W
Scholz
H
H
Stein
B
B
D000241:Adenosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D000242:Cyclic AMP / Q000032:analysis; D004347:Drug Interactions; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011799:Quinazolines / Q000494:pharmacology*; D011983:Receptors, Purinergic / Q000187:drug effects*; D014230:Triazoles / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014970:Xanthines / Q000494:pharmacology*
D011799:Quinazolines; D011983:Receptors, Purinergic; D014230:Triazoles; D014665:Vasodilator Agents; D014970:Xanthines; D019830:Adenosine-5'-(N-ethylcarboxamide); C051360:1,3-dipropyl-8-cyclopentylxanthine; D000242:Cyclic AMP; D000241:Adenosine; D007545:Isoproterenol; C052410:9-chloro-2-(2-furyl)-(1,2,4)triazolo(1,5-c)quinazolin-5-imine