Adenosine receptor interactions alter cardiac contractility in rat heart
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Summary 1. The effect of the adenosine A2 receptor (AdoA2R) agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA) on adenosine A1 receptor (AdoA1R)-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)-N6-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 נpeak systolic developed pressure נdP?/?dtmax), which were significantly attenuated by 1 nmol?/?L DPMA with a shift in pEC50 from 8.0 ᠰ.5 (n = 9) in control hearts to 6.63 ᠱ.03 (n = 5) in treated tissues (P < 0.05). The AdoA2AR antagonist 8-(3-chlorostyryl)caffeine (1 孯l?/?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 AdoA1R-mediated negative inotropic actions, whereas the AdoA2BR antagonist alloxazine (3 孯l?/?L) had no effect on DPMA activity. 4. The results of the present study show that stimulation of the AdoA2R attenuates AdoA1R-dependent reductions in inotropic state. The receptor involved appears to be the AdoA2AR and its action involves stimulation of adenylyl cyclase activity.
Clinical and Experimental Pharmacology & Physiology
© 2010 The Authors and Blackwell Publishing Asia Pty Ltd. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. The definitive version is available at http://onlinelibrary.wiley.com/
Pharmacology and Pharmaceutical Sciences not elsewhere classified