Endocrine regulation of neurotransmitter transporters

Aminergic signalling in the CNS is terminated by clearance of neurotransmit ters from the synapse via high affinity transporter molecules in the presyn aptic membrane. Relatively recent sequence identification of these molecule s has now permitted the initiation of studies of regulation of transporter function at the cellular and systems levels. In vitro studies provide evide nce that the transporters for dopamine, serotonin, and gamma-aminobutyric a cid (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 recogni zed that metabolic hormones such as insulin or the adrenal steroids can hav e 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 activi ty of the transporters. Future studies should permit elucidation of the cel lular basis for endocrine regulation of neurotransmitter clearance, and thu s, the role of endocrines in the maintenance of normal CNS aminergic signal ling. The potential relevance of transporter regulation for the ketogenic d iet is discussed. (C) 1999 Published by Elsevier Science B.V. All rights re served.