Cantharidin and sodium fluoride attenuate the negative inotropic effects of R-PIA in the isolated human atrium

Abstract Cantharidin and sodium fluoride inhibit the activity of serine/threonine protein phosphatases 1 and 2A (PP1, PP2A) Cantharidin or sodium fluoride increase force of contraction in human atrial preparation. R-Phenylisopropyladenosine (R-PIA) is agonistic at A1-adenosine receptors. R-PIA exert negative inotropic effects in human atrium. We hypothesized that cantharidin and sodium fluoride would attenuate negative inotropic effects of R-PIA. During open heart surgery, trabeculae carneae from human right atrium were obtained, human atrial preparations (HAP). These trabeculae were mounted in organ baths and electrically stimulated (one beat per second). We studied further isolated electrically stimulated left atrial preparations (LA) and isolated spontaneously beating right atrial preparations (RA) from wild type mice. Force of contraction was recorded under isometric conditions. R-PIA cumulatively applied exerted rapid sustained monophasic concentration- and time-dependent negative inotropic effects in LA and HAP. These negative inotropic effects of R-PIA were attenuated pre-incubation for 30 minutes with either 100 µM cantharidin or 3 mM sodium fluoride (NaF) in HAP but not in LA. In contrast, the negative chronotropic effects of R-PIA in RA were not attenuated by pre-incubation for 30 minutes with either 100 µM cantharidin or 3 mM sodium fluoride. The A1-adenosine signals in a species specific way in the mammalian heart. We hypothesize that R-PIA may exert a negative inotropic effect via serine/threonine phosphatases in the human atrium.