Endocrine regulation of neurotransmitter transporters

Aminergic signalling in the CNS is terminated by clearance of neurotransmitters from the synapse via high affinity transporter molecules in the presynaptic membrane. Relatively recent sequence identification of these molecules has now permitted the initiation of studies of regulation of transporter function at the cellular and systems levels. In vitro studies provide evidence that the transporters for dopamine, serotonin, and gamma-aminobutyric acid (GABA) may be substrates for regulation by protein kinase C and protein kinase A signalling. Changes in energy balance and metabolic status, such as starvation, result in major shifts in hormonal output. It is now recognized that metabolic hormones such as insulin or the adrenal steroids can have significant acute and chronic effects on several aspects of CNS function. Data from this laboratory and others now provide evidence that insulin and adrenal and gonadal steroid hormones may regulate the synthesis and activity of the transporters. Future studies should permit elucidation of the cellular basis for endocrine regulation of neurotransmitter clearance, and thus, the role of endocrines in the maintenance of normal CNS aminergic signalling. The potential relevance of transporter regulation for the ketogenic diet is discussed.