Norepinephrine transporter (NET)
A protein on nerve cells and adrenal-type tumour cells that pulls noradrenaline back inside after it has been released. A radioactive drug called MIBG looks and acts enough like noradrenaline that this same protein carries it into neuroblastoma and phaeochromocytoma cells, so doctors can see or treat the tumour.
Overview
The norepinephrine transporter is a 12-transmembrane-domain protein of presynaptic sympathetic neurons and adrenal medullary chromaffin cells that terminates noradrenergic signalling by taking norepinephrine back into the cell (uptake-1), an active, sodium- and chloride-dependent, ATP-driven process roughly 50-fold more efficient than passive diffusion. Once inside, norepinephrine (and NET's synthetic analogue metaiodobenzylguanidine, MIBG) can be stored in secretory vesicles via the vesicular monoamine transporters (VMAT1/2) or remain in the cytoplasm.
Tumours that arise from sympathetic neural crest precursors - neuroblastoma, phaeochromocytoma and paraganglioma - retain NET expression at high frequency (around 90% of neuroblastomas are NET-positive), and expression correlates with MIBG avidity on imaging. Radioiodinated MIBG (123I for diagnosis, 131I for therapy) is taken up through NET, giving both a diagnostic scan and, at therapeutic activities, a targeted radiotherapy. Other transporters (OCT1-3, MATE1/2-K) contribute to non-specific uptake into liver, salivary gland and heart and to renal clearance, and drugs that block NET (tricyclic antidepressants, some stimulants) must be stopped before MIBG scanning or therapy because they blunt tumour uptake.
As a target, NET's strength is high, tumour-restricted expression in an otherwise hard-to-image tumour family, plus intracellular retention via VMAT once inside the cell. Its main limitations are heterogeneous expression (MYCN-amplified, poorly differentiated neuroblastomas tend to have lower NET expression and are less MIBG-avid) and competition from other transporters that reduce specificity and complicate dosimetry.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · A protein on nerve cells and adrenal-type tumour cells that pulls noradrenaline back inside after it has been released. A radioactive drug called MIBG looks and acts enough like noradrenaline that this same protein carries it into neuroblastoma and phaeochromocytoma cells, so doctors can see or treat the tumour.
- 1 · What it is
A protein on nerve cells and adrenal-type tumour cells that pulls noradrenaline back inside after it has been released. A radioactive drug called MIBG looks and acts enough like noradrenaline that this same protein carries it into neuroblastoma and phaeochromocytoma cells, so doctors can see or treat the tumour.
- 2 · What goes wrong in cancer
A presynaptic membrane transporter that takes norepinephrine back into sympathetic neurons and adrenal chromaffin cells after release, an active sodium- and chloride-dependent process.
- 3 · How drugs use it
No product in this corpus aims at Norepinephrine transporter (NET) yet. Drugs bind the molecule precisely: to switch it off, flag the cell for the immune system, or deliver a payload.
External identifiers
Biology
A presynaptic membrane transporter that takes norepinephrine back into sympathetic neurons and adrenal chromaffin cells after release, an active sodium- and chloride-dependent process. Tumours arising from sympathetic neural crest precursors (neuroblastoma, phaeochromocytoma, paraganglioma) retain this transporter at high frequency, allowing the norepinephrine analogue MIBG to be carried into tumour cells for imaging and therapy.
- Neuroblastoma: NET-positive in roughly 90% of tumours; MYCN-amplified tumours tend to have lower expression
- Phaeochromocytoma and paraganglioma: NET expressed in chromaffin-derived tumour cells, uptake reinforced by VMAT storage
- Normal sympathetic nerve terminals and adrenal medulla: physiological expression
Latest papers
topQuery for this target: (TITLE:"Norepinephrine transporter" OR ABSTRACT:"Norepinephrine transporter" OR TITLE:"NET" OR ABSTRACT:"NET" OR TITLE:"SLC6A2" OR ABSTRACT:"SLC6A2" OR TITLE:"Noradrenaline transporter" OR ABSTRACT:"Noradrenaline transporter") AND (radiopharmaceutical OR radioligand OR radionuclide OR theranostic OR "nuclear medicine" OR "molecular imaging" OR radiotracer OR scintigraphy OR cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Norepinephrine transporter (NET), not a curated reading list.
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