Why does dopamine levels decrease due to vmat2 inhibition when dopamine is already formed?

Why does dopamine levels decrease due to vmat2 inhibition when dopamine is already formed?

VMAT2 (vesicular monoamine transporter 2) is a protein found in the membrane of vesicles within dopamine-producing neurons. Its main function is to transport dopamine from the cytoplasm of the neuron into vesicles, which protects the dopamine from breakdown by enzymes and allows it to be released into the synapse when the neuron is activated.

When VMAT2 is inhibited by drugs such as reserpine, vesicular uptake of dopamine is blocked, and dopamine is not stored in vesicles as effectively. This results in reduced dopamine release into the synapse and a subsequent decrease in dopamine levels.

It’s important to note that dopamine synthesis is not directly affected by VMAT2 inhibition. Dopamine is still formed in the cytoplasm of the neuron through a series of enzymatic reactions, but without VMAT2 to transport it into vesicles, it is more likely to be degraded by enzymes before it can be released into the synapse.

In summary, VMAT2 inhibition affects dopamine levels by reducing the storage and release of dopamine into the synapse, rather than directly affecting dopamine synthesis.