Neuropeptide receptors represent a large subfamily of GPCRs with 7 transmembrane domains, which can bind various neuropeptides. As neuronal signaling molecules, neuropeptides are used by neurons to communicate with each other to regulate the physiological reactions in specific ways, including metabolism, reproduction, social behaviors, learning, and memory. Neuropeptides receptor family comprises a large number of subtypes, mainly include neuropeptide Y receptors (NPYRs), neuropeptide B/W receptors (NPBWRs), neuropeptide S receptors (NPSRs), and neuropeptide FF receptors (NPFFRs). In human, there have been identified four neuropeptide Y receptors (NPY1R, NPY2R, NPY4R, NPY5R) and everyone can couple to pertussis toxin-sensitive Gi proteins via the inhibition of adenylate cyclase. Activated NPYRs release the Gi subunit which inhibits the production of the second messenger cAMP from ATP. NPBWRs are predominantly expressed in the CNS (substantia nigra and hypothalamus) and in the periphery (reproductive and immune tissues, liver, stomach, and trachea), suggesting a possible role in locomotor control, the release of pituitary hormones, immune reaction and propagation. NPSR is widely distributed in the brain areas (cortex, hypothalamus, amygdala and multiple midline thalamic nuclei), which are functionally associated with emotional behavior, promoting arousal and anxiolytic-like effects. Containing an RF-amide motif which has a high affinity for the pain modulatory peptide neuropeptide NPFF, NPFFRs are believed to be involved in pain modulation, opioid tolerance, cardiovascular regulation, memory and neuroendocrine regulation.
Here show several members of neuropeptide receptors, including NPBWR1, NPBWR2, NPY1R, NPY2R, NPY4R, NPY5R, NPFFR1, NPFFR2, and NPSR1. Different neuropeptide receptor subtypes can have distinct physiological properties and a majority of them are important drug targets for therapies.
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