| Primary Identifier | IPR000986 | Type | Family |
| Short Name | NeuroY6_rcpt |
| description | Neuropeptide Y (NPY) acts as a neurotransmitter in the brain and in the autonomic nervous system. In the brain it is thought to have several functions, including increasing food intake and storage of energy as fat [, , , ], facilitation of learning and memory via the modulation of hippocampal activity [, , ], inhibition of anxiety [, , ], presynaptic inhibition of neurotransmitter release in the CNS and periphery [], and modulation of circadian rhythm [, ]. In the periphery, NPY stimulates vascular smooth muscle contraction [, ], modulates the release of pituitary hormones [, ], pain transmission [], inhibition of insulin release [, , ]and modulation of renal function []. NPY has also been implicated in the pathophysiology of hypertension [], congestive heart failure and appetite regulation [, , , ]and controlling epileptic seizures []. Signalling responses appear to be restricted to certain cell types and in the autonomic system it is mainly produced by neurons of the sympathetic nervous system and serves as a strong vasoconstrictor and also causes growth of fat tissue []. These include inhibition of Ca2+ channels, such as in neurones [], and activation and inhibition of K+ channels, such as in cardiomyocytes []and vascular smooth muscle cells [].The various functions of NPY are mediated by neuropeptide Y receptors, which are members of rhodopsin-like G-protein coupled receptors, they are also activated by peptide YY and the pancreatic polypeptide []. There are five pharmacologically distinct neuropeptide Y receptor subtypes []; neuropeptide Y receptor Y1 (Y1), neuropeptide Y receptor Y2 (Y2), neuropeptide Y receptor Y4 (Y4), neuropeptide Y receptor Y5 (Y5) and neuropeptide Y receptor Y6 (Y6). Four of the neuropeptide Y receptors have been identified in humans (Y1, Y2, Y4, Y5), which represent therapeutic targets for obesity and other disorders [, , ], as they are also involved in the control of circadian rhythm and anxiety [, , , , , ]. The pharmacological profile of the Y6 receptor is controversial, since the 'receptor' is non-functional in primates including humans [, ]and is absent from the rat genome []. All NPY receptors couple to pertussis toxin-sensitive Gi proteins via the inhibition of adenylate cyclase []. Activated neuropeptide receptors release the Gi subunit which inhibits the production of the second messenger cAMP from ATP []. Studies with endogenously expressed receptors have mainly been performed with Y1 receptors and Y2 receptors, whereas investigations of the signal transduction of other natively expressed NPY receptors has as yet, not been demonstrated.This entry represents the neuropeptide Y6 receptor, which shares 60% sequence identity with the Y1 receptor. Its pharmacology resembles that of the Y1 receptor and is distinct from that described for Y2, Y3 and Y4 receptors []. In mice, the Y6 receptor is expressed within discrete regions of the hypothalamus, including the suprachiasmatic nucleus, anterior hypothalamus, bed nucleus stria terminalis, and the ventromedial nucleus, with no localisation apparent elsewhere in the brain; and in the testis. The absence of this protein leads to major reduction in bone mass without modifying bone length [, , ]. |
