Adenosine receptor interactions alter cardiac contractility in rat heart

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Title Adenosine receptor interactions alter cardiac contractility in rat heart
Author Rose'Meyer, Roselyn Barbara
Journal Name Clinical and Experimental Pharmacology & Physiology
Year Published 2010
Place of publication Australia
Publisher Wiley-Blackwell Publishing Asia
Abstract 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 × peak systolic developed pressure × dP / dtmax), which were significantly attenuated by 1 nmol / L DPMA with a shift in pEC50 from 8.0 ± 0.5 (n = 9) in control hearts to 6.63 ± 1.03 (n = 5) in treated tissues (P < 0.05). The AdoA2AR antagonist 8-(3-chlorostyryl)caffeine (1 μmol / 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 μmol / 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.
Peer Reviewed Yes
Published Yes
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Copyright Statement Copyright 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
Volume 37
Issue Number 1
Page from 46
Page to 50
ISSN 0305-1870
Date Accessioned 2010-12-22
Language en_AU
Research Centre Menzies Health Institute Qld; Heart Foundation Research Centre
Faculty Griffith Health Faculty
Subject Pharmacology and Pharmaceutical Sciences
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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