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Cardiovascular Division, Department of Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104
Activation of P2 purinergic
receptors exerts a potent positive inotropic effect in the cardiac
myocyte. However, it is unknown whether its activation can also cause
an increased contractility in intact heart. With the use of isolated
rat and mouse hearts, the objective of the present study was to
investigate the effect of P2 receptor agonist on the function of the
intact heart. In both Langendorff rat hearts and working rat and mouse
heart models, the P2X receptor agonist 2-methylthio-ATP (2-meSATP)
caused dose-dependent increases in left ventricular developed pressure,
rate of contraction, and rate of relaxation. The extent of P2X receptor
agonist-stimulated increase in contractility was significantly less
than that stimulated by the 
-adrenergic agonist isoproterenol.
However, the increase in contractility occurred without a significant
effect on the basal heart rate, in contrast to that caused by
isoproterenol. In isolated rat ventricular myocytes, both ATP and the
P2X receptor agonist 2-meSATP stimulated large increases in the myocyte
contractile amplitude (107 ± 13% and 99 ± 9%,
n = 17 cells from 5 rats and n = 19 cells from 6 rats, respectively). 2-meSATP caused only a slight
increase in phospholipase C activity and could stimulate myocyte
contractility in the presence of phospholipase C inhibitor U-73122,
consistent with the role of a phospholipase C-independent P2X receptor
in mediating the positive inotropic effect of 2-meSATP. The data
provide evidence for a potentially important physiological role of the
cardiac P2X receptor and for the concept that agonist at this receptor
may be beneficial for the treatment of cardiac dysfunction.
heart; drugs; ATP; purines; inotropy
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