Neurotensin receptors are transmembrane receptors that bind the neurotransmitter neurotensin. Two of the receptors encoded by the NTSR1 and NTSR2 genes contain seven transmembrane helices and are G protein coupled. The third receptor has a single transmembrane domain and is encoded by the SORT1 gene. Neurotensin (NTS) is a 13-amino-acid peptide that functions as both a neurotransmitter and a hormone through the activation of the neurotensin receptor NTSR1, a G-protein-coupled receptor (GPCR). In the brain, NTS modulates the activity of dopaminergic systems, opioid-independent analgesia, and the inhibition of food intake; in the gut, NTS regulates a range of digestive processes.
An Overview of Neurotensin Receptor
Neurotensin (NTS) was inadvertently obtained by American physiologists Carraway and Leeman in 1973 when they isolated bovine substance P (SP). NTS was widely expressed in central nervous system (CNS) and peripheral nervous system (PNS) in human and animal. Recent studies have shown that NTS is highly expressed in many kinds of tumor tissues and cells, and has carcinogenic effect. The signal pathway mediated by NTS and its main receptor NTSR1 can obviously promote the development of tumor, mainly because NTS provides a growth signal for malignant tumor and promotes its proliferation.
Major Types of Neurotensin Receptor
The physiological functions of NTS are mainly mediated by its binding neurotensin receptor (NTSRs), and there are three known receptors, NTSR1, NTSR2 and NTSR3, respectively. Among them, NTSR1 and NTSR2 are NTS specific receptors, which belong to G-protein-coupled receptors (GPCRs) and have seven transmembrane regions. However, NTS is highly compatible with NTSR1, but with low affinity to NTSR2. NTSR3 is encoded by SORT1 gene. Therefore, NTSR3, also known as sortilin, is the only single transmembrane receptor of all neuropeptide receptors.
Agonists and Inhibitors of Neurotensin Receptor
PD149163 is a compound that acts on the central temperature receptor. It is also a selective neurotensin receptor 1 agonist. PD149163 can penetrate the blood-brain barrier and produce a series of central nervous system effects after peripheral administration, such as effects of promoting cognitive, antipsychotic, anti-anxiety and reducing food intake. It can also effectively induce the production of regulatory hypothermia in rats. In addition, SR48692, a specific antagonist of NTSR1, can competitively block the physiological effects mediated by NTSR1.
Neurotensin Receptorand Diseases
NT and NTR1 play a certain role in the occurrence, development and prognosis of various malignant tumors. Clinical information analysis showed that the expression of NT and NTR1 in breast infiltrating ductal carcinoma patients with NTR1 expression promoted the growth and proliferation of breast cancer cells, and enhanced tumor invasion and metastasis ability.