Rose'meyer RB
Adenosine receptor interactions alter cardiac contractility in the rat heart. [JOURNAL ARTICLE]
Clin Exp Pharmacol Physiol 2009 Jun 29.
1. The effect of an adenosine (Ado) A(2) receptor agonist, N(6)-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA) on AdoA(1) receptor mediated negative inotropic responses was investigated in rat heart. 2. Hearts from male Wistar rats (250-350g) 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 mins equilibration (R)-N(6)-phenylisopropyl adenosine (R-PIA) concentration-response curves were acquired in the absence or presence of DPMA. 3. R-PIA induced concentration-dependent decreases in triple product (HR x left ventricular developed pressure x dP/dt(max)) in paced hearts. DPMA (1 nM) significantly attenuated R-PIA induced decreases in triple product, with a shift in pEC(50) from 8.0 +/- 0.51 (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 muM) and the adenylyl cyclase inhibitor cis-N-(2-phenylcyclopentyl)-azacyclotridec-1-en-2-amine hydrochloride (MDL12330A, 100nM) reversed the effect of DPMA on AdoA(1)R mediated negative inotropic actions while the adoA(2B)R inhibitor (alloxazine, 3 muM) had no effect on DPMA activity. 4. The results show that stimulation of AdoA(2)R attenuates AdoA(1)R dependent reductions in inotropic state. The adenosine receptor sub-type involved appears to be the AdoA(2A)R, and its action involves stimulation of adenylyl cyclase activity.
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