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Neurotensin Receptor Family

Neurotensin is a brain and gastrointestinal tridecapeptide that mediates its central and peripheral effects through interaction with three identified neurotensin receptors referred to as NTSR1, NTSR2, and NTSR3 (also known as Sortilin 1). NTSR1 and NTSR2 belong to rhodopsin-like GPCRs family with a common structural framework comprising 7 transmembrane (TM) helices, while NTSR3 is a single transmembrane receptor. NTSR1 is expressed predominantly in the brain and gastrointestinal tract, e.g., in the diagonal band of Broca, medial septal nucleus, nucleus basalis magnocellularis, suprachiasmatic nucleus, supramammillary area, substantia nigra and ventral tegmental area. The receptor is also expressed in the dorsal root ganglion neurons of the spinal cord. NTSR1 is a Gq-preferring receptor, which can activate phospholipase C, causing an increase of intracellular calcium levels. Research shows that NTSR1 is associated with multiple biological functions, such as low blood pressure, high blood sugar, low body temperature, antinociception, and regulation of intestinal motility and secretion. Higher levels of expression of the NTSR2 are found in some brain regions, including the olfactory system, cerebral and cerebellar cortices, hippocampus and hypothalamic nuclei. The receptor has also been found at lower levels in the kidney, uterus, heart, and lung. With high sensitivity to antihistamine levocabastine, NTSR2 can couple to phospholipase C, phospholipase A2 and MAP kinase. NTSR2 contributes to the protective effect of neurotensin on pancreatic beta cells.

Here show the cardinal members of neurotensin receptors, including NTSR1 with high neurotensin-affinity and NTSR2 with low neurotensin-affinity but high levocabastine-affinity. The regulation of NTSR1 expression can occur at transcriptional or post-transcriptional levels. The NTSR2 expression is increased in response to some environmental irritants or agonists.

Human Neurotensin Receptors Members
NTSR1 NTSR2

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