title: Regulation of the norepinephrine transporter by endothelins: a potential therapeutic target.
abstract: Neuronal norepinephrine (NE) uptake is a crucial step in noradrenergic neurotransmission that regulates NE concentration in the synaptic cleft. It is a key mechanism mediated by the NE transporter (NET) which takes the neurotransmitter into the presynaptic neuron terminal or the adrenal medulla chromaffin cell. The activity of NET is short and long terms modulated by phosphorylation mediated by protein kinases A, C, and G and calcium-calmodulin-dependent protein kinase, whereas the transporter availability at the cell surface is regulated by glycosylation. Several neuropeptides like angiotensins II, III, and 1-7, bradykinin, natriuretic peptides, as well as endothelins (ETs) regulate a wide variety of biological effects, including noradrenergic transmission and in particular neuronal NE uptake. Diverse reports, including studies from our laboratory, show that ETs differentially modulate the activity and expression of NET not only in normal conditions but also in diverse cardiovascular diseases such as congestive heart failure and hypertension. Current literature supports a key role for the interaction between ETs and NE in maintaining neurotransmission homeostasis and further suggests that this interaction may represent a potential therapeutic target for various diseases, particularly hypertension.
authors.affiliation: Cátedra de Fisiología e Instituto de la Química y Metabolismo del Fármaco (IQUIMEFA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina. Electronic address: mvatta@ffyb.uba.ar.
authors.forename: Marcelo S
authors.initials: MS
authors.lastname: Vatta
authors.affiliation: Cátedra de Fisiopatología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Instituto de Inmunología, Genética y Metabolismo (INIGEM-CONICET), Buenos Aires, Argentina.
authors.forename: Liliana G
authors.initials: LG
authors.lastname: Bianciotti
authors.affiliation: Cátedra de Fisiología e Instituto de la Química y Metabolismo del Fármaco (IQUIMEFA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: María J
authors.initials: MJ
authors.lastname: Guil
authors.affiliation: Cátedra de Fisiología e Instituto de la Química y Metabolismo del Fármaco (IQUIMEFA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Sandra I
authors.initials: SI
authors.lastname: Hope
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000378:metabolism; D016232:Endothelins / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D009638:Norepinephrine / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D016232:Endothelins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D009638:Norepinephrine
keywords: Endothelins; Neuronal norepinephrine uptake; Neuropeptides; Norepinephrine inactivation; Norepinephrine transporter