HGNC Approved Gene Symbol: NPY2R
Cytogenetic location: 4q32.1 Genomic coordinates (GRCh38): 4:155,173,723-155,217,076 (from NCBI)
Neuropeptide Y (NPY) signals through a family of G protein-coupled receptors present in the brain and sympathetic neurons. At least 3 types of neuropeptide Y receptor have been defined on the basis of pharmacologic criteria, tissue distribution, and structure of the encoding gene; see 162641 and 162643. Rose et al. (1995) reported the expression cloning in COS cells of a cDNA for the human type 2 receptor, NPY2R. Transfected cells showed high affinity for NPY (162640), peptide YY (PYY; 600781), and a fragment of NPY including amino acids 13 to 36. The predicted 381-amino acid protein has 7 transmembrane domains characteristic of G protein-coupled receptors and is only 31% identical to the human Y1 receptor (NPY1R; 162641). A 4-kb mRNA was detected on Northern blots of tissue samples from several regions of the nervous system.
Gerald et al. (1995) cloned the cDNA corresponding to the human Y2 receptor from a human hippocampal cDNA expression library using a radiolabeled PYY-binding assay. They expressed the Y2 gene in COS-7 cells and performed a hormone-binding assay which showed that the Y2 receptor binds (from highest to lowest affinity) PYY, NPY, and pancreatic polypeptide (PP; 167780) hormones.
Ammar et al. (1996) cloned and characterized the human gene encoding the type 2 NPY receptor.
Ammar et al. (1996) found that the human NPY2R gene spans 9 kb of genomic sequence and comprises 2 exons. As in the type 1 NPY receptor gene, the 5-prime untranslated region of NPY2R is interrupted by a 4.5-kb intervening sequence.
Ammar et al. (1996) demonstrated by Southern analysis of rodent-human cell hybrids followed by fluorescence in situ hybridization (FISH) that the NPY2R gene maps to 4q31, the same region containing the NPY1R gene, suggesting that these subtypes may have arisen by gene duplication despite their structural differences.
By interspecific backcross analysis, Lutz et al. (1997) mapped the Npy1r and Npy2r genes to conserved linkage groups on mouse chromosomes 8 and 3, respectively, which correspond to the distal region of human chromosome 4q.
Lovelace et al. (2023) found that vagal sensory neurons (VSNs) expressed Npy2r and predominately connected the heart ventricular wall to the area postrema in mice. Optogenetic activation of Npy2r VSNs elicited the classic triad of Bezold-Jarisch reflex (BJR) responses, characterized by hypotension, bradycardia, and suppressed respiration, leading to fainting. Animals also displayed a range of phenotypes reflected in clinical syncope, including reduced cardiac output, cerebral hypoperfusion, pupil dilation, and eye-roll. Activation of Npy2r VSNs also caused suppression of activity across a large distributed neuronal population that could not be explained by changes in spontaneous behavioral movements. Moreover, bidirectional manipulation of the periventricular zone had a push-pull effect, with inhibition leading to longer syncope periods and activation inducing arousal. Deletion of Npy2r VSNs abolished the Bezold-Jarisch reflex, confirming that VSNs mediated the Bezold-Jarisch reflex and induced syncope.
Ammar, D. A., Eadie, D. M., Wong, D. J., Ma, Y.-Y., Kolakowski, L. F., Jr., Yang-Feng, T. L., Thompson, D. A. Characterization of the human type 2 neuropeptide Y receptor gene (NPY2R) and localization to the chromosome 4q region containing the type 1 neuropeptide Y receptor gene. Genomics 38: 392-398, 1996. [PubMed: 8975716] [Full Text: https://doi.org/10.1006/geno.1996.0642]
Gerald, C., Walker, M. W., Vaysse, P. J.-J., He, C., Branchek, T. A., Weinshank, R. L. Expression cloning and pharmacological characterization of a human hippocampal neuropeptide Y/peptide YY Y2 receptor subtype. J. Biol. Chem. 270: 26758-26761, 1995. [PubMed: 7592910] [Full Text: https://doi.org/10.1074/jbc.270.45.26758]
Lovelace, J. W., Ma, J., Yadav, S., Chhabria, K., Shen, H., Pang, Z., Qi, T., Sehgal, R., Zhang, Y., Bali, T., Vaissiere, T., Tan, S., Liu, Y., Rumbaugh, G., Ye, L., Kleinfeld, D., Stringer, C., Augustine, V. Vagal sensory neurons mediate the Bezold-Jarisch reflex and induce syncope. Nature 623: 387-396, 2023. [PubMed: 37914931] [Full Text: https://doi.org/10.1038/s41586-023-06680-7]
Lutz, C. M., Frankel, W. N., Richards, J. E., Thompson, D. A. Neuropeptide Y receptor genes on human chromosome 4q31-q32 map to conserved linkage groups on mouse chromosomes 3 and 8. Genomics 41: 498-500, 1997. Note: Erratum: Genomics 44: 251-252, 1997. [PubMed: 9169155] [Full Text: https://doi.org/10.1006/geno.1997.4698]
Rose, P. M., Fernandes, P., Lynch, J. S., Frazier, S. T., Fisher, S. M., Kodukula, K., Kienzle, B., Seethala, R. Cloning and functional expression of a cDNA encoding a human type 2 neuropeptide Y receptor. J. Biol. Chem. 270: 22661-22664, 1995. Note: Erratum: J. Biol. Chem. 270: 29038 only, 1995. [PubMed: 7559383] [Full Text: https://doi.org/10.1074/jbc.270.39.22661]