The adenosine A_2A receptor ( A_2AR) enhances cardiac contractility and the adenosine A₁R receptor (A₁R) is antiadrenergic by reducing the adrenergic 1 receptor (₁R)-elicited increase in contractility. In this study we compared the A_2AR-, A₁R- and ₁R-elicited actions on isolated rat ventricular myocytes in terms of calcium transient and contractile responses involving protein kinase A (PKA) and protein kinase C (PKC). Stimulation of A_2AR with 2 µM (~EC₅₀) 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 V_max of shortening (+MVS) and relaxation (-MVS) by 31-34% with no change in time-to-50% relengthening (TTL). 1R stimulation using 2 nM (~EC₅₀) isoproterenol (ISO) increased CTR, +MVT, -MVT by 67-162% and decreased TTR by 43%. ISO increased MSS, +MVS, -MVS by 153-174% and decreased TTL 31%. The A_2AR and ₁R Ca transient and contractile responses were not additive. The PKA inhibitor Rp-cAMPS prevented both the CGS and ISO-elicited contractile responses. The PKC inhibitors chelerythrine and KIE1-1 peptide (PKC specific) prevented the antiadrenergic action of A₁R, but did not influence in A_2AR-mediated increases in contractile variables. The findings suggest that cardiac A_2AR utilize cAMP/PKA like ₁R, but the Ca transient and contractile responses are less in magnitude and not equally affected. While PKC is important in the A₁R antiadrenergic action, it does not seem to play a role in the A_2AR-elicited Ca transient and contractile events.