Adenosine A2Aand β-adrenergic calcium transient and contractile responses in rat ventricular myocytes

Abstract

The adenosine A2Areceptor (A2AR) enhances cardiac contractility, and the adenosine A1R receptor (A1R) is antiadrenergic by reducing the adrenergic β1receptor (β1R)-elicited increase in contractility. In this study we compared the A2AR-, A1R-, and β1R-elicited actions on isolated rat ventricular myocytes in terms of Ca transient and contractile responses involving PKA and PKC. Stimulation of A2AR with 2 μM (∼EC50) CGS-21680 (CGS) produced a 17–28% increase in the Ca transient ratio (CTR) and maximum velocities ( Vmax) 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). β1R stimulation using 2 nM (∼EC50) 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 A2AR and β1R 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 (PKCε specific) prevented the antiadrenergic action of A1R but did not influence A2AR-mediated increases in contractile variables. The findings suggest that cardiac A2AR utilize cAMP/PKA like β1R, 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 A2AR-elicited Ca transient and contractile events.