Regulation of the Norepinephrine Transporter by Endothelins: A Potential Therapeutic Target

VATTA MS; BIANCIOTTI LG; GUIL MJ; HOPE S

VITAMINS AND HORMONES SERIES

ELSEVIER ACADEMIC PRESS INC

Lugar: Burlington, MA, Estados Unidos; Año: 2015 vol. 28 p. 371 - 405

0083-6729

Neuronal norepinephrine (NE) uptake is a crucial step in noradrenergic neurotransmissionthat regulates NE concentration in the synaptic cleft. It is a key mechanism mediatedby the NE transporter (NET) which takes the neurotransmitter into the presynapticneuron terminal or the adrenal medulla chromaffin cell. The activity of NET is short andlong terms modulated by phosphorylation mediated by protein kinases A, C, and G andcalcium?calmodulin-dependent protein kinase, whereas the transporter availability atthe cell surface is regulated by glycosylation. Several neuropeptides like angiotensinsII, III, and 1?7, bradykinin, natriuretic peptides, as well as endothelins (ETs) regulate a wide variety of biological effects, including noradrenergic transmission and in particularneuronal NE uptake. Diverse reports, including studies from our laboratory, show thatETs differentially modulate the activity and expression of NET not only in normal conditionsbut also in diverse cardiovascular diseases such as congestive heart failure andhypertension. Current literature supports a key role for the interaction between ETs andNE in maintaining neurotransmission homeostasis and further suggests that this interactionmay represent a potential therapeutic target for various diseases, particularlyhypertension.