Adenosine A2A and β-adrenergic calcium transient and contractile responses in rat ventricular myocytes

Dobson JG Jr, Shea LG, Fenton RA. Adenosine A(2A) and beta-adrenergic calcium transient and contractile responses in rat ventricular myocytes. Am J Physiol Heart Circ Physiol 295: H2364-H2372, 2008. First published October 10, 2008; doi: 10.1152/ajpheart. 00927.2008.-The adenosine A2A receptor (A(2A)R) enhances cardiac contractility, and the adenosine A(1)R receptor (A(1)R) is antiadrenergic by reducing the adrenergic beta(1) receptor (beta(1)R)-elicited increase in contractility. In this study we compared the A(2A)R-, A(1)R-, and beta(1)R-elicited actions on isolated rat ventricular myocytes in terms of Ca transient and contractile responses involving PKA and PKC. Stimulation of A(2A)R with 2 mu M (similar to EC(50)) CGS-21680 (CGS) produced a 17-28% increase in the Ca transient ratio (CTR) and maximum velocities (V(max)) of transient ratio increase (+ MVT) and recovery (-MVT) but no change in the time-to-50% recovery (TTR). CGS increased myocyte sarcomere shortening (MSS) and the maximum velocities of shortening (+ MVS) and relaxation (-MVS) by 31-34% with no change in time-to-50% relengthening (TTL). beta(1)R stimulation using 2 nM (similar to EC(50)) isoproterenol (Iso) increased CTR, +MVT, and-MVT by 67-162% and decreased TTR by 43%. Iso increased MSS, +MVS, and-MVS by 153-174% and decreased TTL by 31%. The A(2A)R and beta(1)R Ca transient and contractile responses were not additive. The PKA inhibitor Rp-adenosine 3', 5'-cyclic monophosphorothioate triethylamonium salt prevented both the CGS-and Iso-elicited contractile responses. The PKC inhibitors chelerythrine and KIE1-1 peptide (PKC epsilon specific) prevented the antiadrenergic action of A1R but did not influence A(2A)R-mediated increases in contractile variables. The findings suggest that cardiac A(2A)R utilize cAMP/PKA like beta(1)R, but the Ca transient and contractile responses are less in magnitude and not equally affected. Although PKC is important in the A1R antiadrenergic action, it does not seem to play a role in A(2A)R-elicited Ca transient and contractile events.