Preventing the cardiotoxic effects of norepinephrine (NE), excessive sympathetic activation, has been a critical goal in the treatment of myocardial infarction, congestive heart failure, and hypertension. Corti et al. investigated the role of E-NTPDase1/CD39, an ecto-ATPase that catabolizes extracellular ATP, as a modulator of the autocrine effects of transmitter ATP at sympathetic nerve terminals. Silencing of E-NTPDase1/CD39 in PC12 cells increased the depolarization-induced exocytosis of ATP and dopamine and increased ATP-induced dopamine release. Overexpression of E-NTPDase1/CD39 resulted in enhanced removal of ATP, decreased exocytosis of ATP and dopamine, and a large decrease in the ATP-induced dopamine release. Ischemia produced effects similar to those seen with depolarization of PC12 cells in both cells lacking or overexpressing E-NTPDase1/CD39. These results demonstrate that E-NTPDase1/CD39 plays a major role at sympathetic nerve terminals as a modulator of the release and effects of ATP and NE. Modulation by E-NTPDase1/CD39 occurs whether ATP is released by neuronal depolarization or ischemia and even suggests that recombinant E-NTPDase1/CD39 may be used therapeutically in myocardial ischemia to reduce cardiac dysfunctions due to excessive catecholamine release.
See article at J Pharmacol Exp Ther 2011, 337:524–532
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