Neurotensin (NT) initiates an intracellular response by interacting with the G protein-coupled receptors NTR1 (NTS1 receptor, high affinity NTR) and NTR2 (NTS2 receptor, levocabastine-sensitive neurotensin receptor), and the type I receptor NTR3 (NTS3 receptor, sortilin-1, Gp95). NT has a wide distribution in regions of the brain and in peripheral tissues where NT receptors can contribute to hypotension, hyperglycemia, hypothermia, antinociception and regulation of intestinal motility and secretion. HL-60 cells express NTR1, which can couple to Gq, Gi/o or Gs. Alternative splicing of rat NTR2 can generate a 5-transmembrane domain variant isoform that is coexpressed with the full length NTR2 throughout the brain and spinal cord. NTR3 activation in the murine microglial cell line N11 induces MIP-2, MCP-1, IL-1beta and TNFalpha in an ERK1/2 and Akt kinase-dependent manner.
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