Adenosine receptor interactions alter cardiac contractility in rat heart.
1. The effect of the adenosine A(2) receptor (AdoA(2)R) agonist N(6)-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA) on adenosine A(1) receptor (AdoA(1)R)-mediated negative inotropic responses was investigated in rat heart. 2. Hearts from male Wistar rats (250-350 g) were perfused with Krebs'-Henseleit solution at constant flow in non-recirculating Langendorff mode. Hearts were paced at 5 Hz (5 ms duration, supramaximal voltage) via ventricular electrodes. After 30 min equilibration, (R)-N(6)-phenylisopropyl adenosine (R-PIA) concentration-response curves were constructed in the absence or presence of DPMA. 3. In paced hearts, R-PIA induced concentration-dependent decreases in triple product (heart rate x peak systolic developed pressure x dP / dt(max)), which were significantly attenuated by 1 nmol / L DPMA with a shift in pEC(50) from 8.0 +/- 0.5 (n = 9) in control hearts to 6.63 +/- 1.03 (n = 5) in treated tissues (P < 0.05). The AdoA(2A)R antagonist 8-(3-chlorostyryl)caffeine (1 micromol / L) and the adenylyl cyclase inhibitor cis-N-(2-phenylcyclopentyl)-azacyclotridec-1-en-2-amine hydrochloride (MDL12330A; 100 nmol / L) reversed the effects of DPMA on AdoA(1)R-mediated negative inotropic actions, whereas the AdoA(2B)R antagonist alloxazine (3 micromol / L) had no effect on DPMA activity. 4. The results of the present study show that stimulation of the AdoA(2)R attenuates AdoA(1)R-dependent reductions in inotropic state. The receptor involved appears to be the AdoA(2A)R and its action involves stimulation of adenylyl cyclase activity.
Rose'Meyer
Roselyn B
RB
School of Medical Sciences, Griffith University, Queensland, Australia. r.rosemeyer@griffith.edu.au
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000502:physiology; D000818:Animals; D002110:Caffeine / Q000031:analogs & derivatives / Q000494:pharmacology; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005415:Flavins / Q000494:pharmacology; D007097:Imines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D010660:Phenylisopropyladenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000187:drug effects / Q000502:physiology*; D043683:Receptors, Adenosine A2 / Q000502:physiology*; D013268:Stimulation, Chemical
D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000067956:Adenylyl Cyclase Inhibitors; D004791:Enzyme Inhibitors; D005415:Flavins; D007097:Imines; D043682:Receptor, Adenosine A1; D043683:Receptors, Adenosine A2; C056426:CGS 24012; C081320:8-(3-chlorostyryl)caffeine; D010660:Phenylisopropyladenosine; D002110:Caffeine; C008173:isoalloxazine; C014925:RMI 12330A; D000262:Adenylyl Cyclases; D000241:Adenosine