Reverse transport
Reverse transport, or transporter reversal, is a phenomenon in which the substrates of a membrane transport protein are moved in the opposite direction to that of their typical movement by the transporter. Transporter reversal typically occurs when a membrane transport protein is phosphorylated by a particular protein kinase, which is an enzyme that adds a phosphate group to proteins.
The primary function of most neurotransmitter transporters is to facilitate neurotransmitter reuptake. During neurotransmitter reuptake, neurotransmitter transporters will move specific types of neurotransmitters from the extracellular space into the cytosol of a neuron or glial cell. When these transporters operate in reverse, they produce neurotransmitter efflux. In neurons, transporter reversal facilitates the release of neurotransmitters into the synaptic cleft, resulting in a higher concentration of synaptic neurotransmitters and increased signaling through the corresponding neurotransmitter receptors.
For example, monoamine releasing agents, such as amphetamines, produce cytosolic neurotransmitter efflux by triggering reverse transport at vesicular monoamine transporters and other monoamine transporters that are located along the plasma membrane of neurons. The precise mechanisms by which amphetamines and other monoamine releasing agents mediate induction of reverse transport are poorly understood. Protein kinase C and Ca2+/calmodulin-dependent [protein kinase II alpha|Ca2+/calmodulin-dependent protein kinase II alpha] have been shown experimentally to phosphorylate monoamine transporters and promote reverse transport after amphetamine exposure.