THE (Na+ + K+)ATPase, an integral membrane protein located in virtually all animal cells, couples the hydrolysis of ATP to the countertransport of Na+ and K+ ions across the plasma membrane1,2. In neurons, a large portion of cellular energy is expended by this enzyme to maintain the ionic gradients that underlie resting and action potentials. Although neurotransmitter regulation of the enzyme in brain has been reported3,4, such regulation has been characterized either as a nonspecific phenomenon5,6 or as an indirect effect of neurotransmitter-induced changes in ionic gradients7. We report here that the neurotransmitter dopamine, through a synergistic effect on D1 and D2 receptors, inhibits the (Na+ + K+)ATPase activity of isolated striatal neurons. Our data provide unequivocal evidence for regulation by a neurotransmitter of a neuronal ion pump. They also demonstrate that synergism between D1 and D2 receptors, which underlies many of the electrophysical and behavioural effects of dopamine in the mammalian brain8, can occur on the same neuron. In addition, the results support the possibility that dopamine and other neurotransmitters can regulate neuronal excitability through the novel mechanism of pump inhibition.
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Bertorello, A., Hopfield, J., Aperia, A. et al. Inhibition by dopamine of (Na+ + K+)ATPase activity in neostriatal neurons through D1 and D2 dopamine receptor synergism. Nature 347, 386–388 (1990). https://doi.org/10.1038/347386a0
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