( s. The neurotransmitter therefore plays...)Discovery of New Dopamine Action May Yield Alternative Psychiatric Drugs

Neurotransmitters such as dopamine are chemical messengers that one neuron launches at receptors on another to trigger a nerve impulse in the receiving neuron. Receptors are protein switches on the surfaces of neurons that recognize neurotransmitters and translate their signals into a cellular response. Dopamine exerts its functions in the brain by binding to two broad classes of receptors -- one class that transmits signals fast and another that acts through signaling pathways to relay messages more slowly.

Dopamine receptors exist in two forms, D1 and D2 class receptors, both belonging to a class of slow-acting receptors known as G protein-coupled receptors. One method by which dopamine relays messages to the brain over a period of minutes has been well worked out. The new study by Caron and his colleagues reveals a second mechanism whereby chronic dopamine affects the brain, perhaps indefinitely.

The Duke team's previous work suggested that the regulatory protein beta-arrestin 2, normally involved in desensitization of receptor signals, is required for normal dopamine-related behavior. They also found that prolonged stimulation of D2 receptors leads to inactivation of a regulatory protein called Akt.

Furthermore, they showed, Akt inactivation occurred more slowly and was maintained for longer than other similar biochemical events that had previously been observed. However, the mechanism behind that inactivation remained unclear.

In the current study in mice, the Duke team found that Akt inactivation by dopamine involves the formation of a previously unidentified complex containing beta-arrestin 2, Akt and a third protein phosphatase 2A that inactivates Akt. Mice lacking beta-arrestin become less responsive to certain drugs and exhibit abnormalities in behaviors, such as locomotion, associated with dopamine. In addition
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Source:DukeHealth