Neuropeptide Y Family Related Drug Discovery Products
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A 36-residue peptide amide, neuropeptide Y (NPY) was first discovered in the pig brain. It is broadly dispersed throughout the central and peripheral nervous systems and is the most abundant peptide found in mammalian brains. The grouping of these hormones as a family of homologous hormones is based on the primary structural homology of NPY with peptide YY (PYY) recovered from the intestine and the pancreatic polypeptide (PP) separated from the pancreas, as well as the overlap of their physiological activity. In sympathetic nerve fibers that innervate different organs, NPY is typically found co-stored and co-released with noradrenaline in the periphery. In reaction to food stimuli, PYY and PP, which are located in the endocrine cells of the intestine and pancreas, respectively, are released.
To meet the needs of our customers, Creative Biolabs can offer neuropeptide Y family related products to contribute to the success of drug discovery:
Overview of Neuropeptide Y Family
- NPY1R
The 384 amino acid Y1 receptor's natural agonists are NPY and PYY. The Y1 receptor can be endogenously and non-subtype selectively activated by NPY, and it shares approximately 92% of its sequence with orthologs found in mouse, rat, pig, guinea pig, and cow. The Y1 receptor was mostly expressed in the thalamus, neocortex, hypothalamus, and hippocampal regions of the body. The colonic epithelium, mucosal nerve, heart, adrenal gland, kidney, and placenta all express the Y1 receptor in humans.
- NPY2R
The preferred agonists of the 381 amino acid long hY2 receptor are NPY and PYY. Although it has a relatively lesser affinity for PP, this receptor has significant affinity for pairing with NPY and PYY. Presynaptically, the hY2 receptor is mostly found in central neuronal tissue such the brain, hippocampus, thalamus, hypothalamus, and some regions of the peripheral nervous system.
- NPY4R
The Y4 receptor is the only subtype in the family that has a preference for PP, though it can also be partially triggered by PYY and NPY. When compared to other Y receptor subtypes, Y4 has the least sequence similarity (less than 86% with that of its orthologues). The Y4 receptor has so far been identified in the human epidermis, liver, prostate, central nervous system, and gastrointestinal tract. It is made up of 375 amino acids.
- NPY5R
Equal sensitivities are displayed by the Y5 receptor for hNPY, hPYY, and hPP. The third intracellular loop (ICL3) of the Y5 receptors, which has 140 amino acids, is significantly bigger than that of other Y receptor family members, while the C-terminus is significantly shorter. The Y5 receptor is primarily expressed in the central nervous system, including the thalamus, temporal cortex, hypothalamus, and amygdala. It is highly conserved and has more than 85% sequence homology to its orthologues.
Fig.1. Schematic of the possible role of members of the NPY family in the pathophysiology of IBD. (El-Salhy & Hausken, 2016)
Neuropeptide Y Family Drug Discovery
It has been demonstrated that NPY interacts with a few different receptor classes, both in vitro and in vivo. However, more research is still needed to fully understand the mechanisms and pathways that underlie the various processes and tasks that NPY receptors carry out in various organs and tissues. Studies in this field may offer new insight into novel treatment options for these kinds of diseases. Additionally, the potential roles of NPY receptors in the browning of white adipocyte tissue and metabolism disorders like diabetes, obesity, and hypertension also need to be clarified. Therefore, additional research and efforts should focus on identifying high affinity and particular NPY receptors as possible therapeutic agents.
Reference
- El-Salhy, M.; Hausken, T. The role of the neuropeptide Y (NPY) family in the pathophysiology of inflammatory bowel disease (IBD). Neuropeptides. 2016, 55: 137-144.
