Disease relevance of NPY1R

• EXPERIMENTAL DESIGN: Fifteen adrenal cortical tumors, 20 paragangliomas, 23 pheochromocytomas, 20 neuroblastomas, and 8 normal adrenal glands were investigated by in vitro NPY receptor autoradiography using 125I-labeled peptide YY in competition experiments with receptor subtype selective analogs [1].
• The high frequency of NPY receptors in steroid hormone-producing ovarian sex cord-stromal tumors, together with the known influence of NPY on steroid hormone and catecholamine secretion in the rodent adrenal gland, led to the investigation of NPY receptor expression in the human adrenal gland and related tumors [1].
• NPY receptor agonists may prove beneficial in the treatment of the congested nose in allergic or vasomotor rhinitis [2].
• Cyclogues (contraction of cyclic analogues), which were approximately one-half the size of native NPY, were initially screened for binding affinity at two discrete NPY receptor types using human neuroblastoma cell membranes, SK-N-MC and SK-N-BE2 [3].
• In NPY1 receptor injected cells neuropeptide Y (100 nM) caused a 53 +/- 10 nA inward current (n = 14; EC50 = 3 nM) and this effect was blocked by pertussis toxin (500 ng ml-1 24 h) [4].

Psychiatry related information on NPY1R

• The significance of different NPY receptor subtypes controlling estrous and feeding behavior is highlighted by results on expression of Fos immunoreactivity (Fos-IR) elicited by either PYY-(3-36) or [Leu(31),Pro(34)]PYY at a dose of each that differentiated between the two behaviors [5].

High impact information on NPY1R

• Given that mRNA for the cloned Y5 receptor is apparently restricted to the CNS, Angela Bischoff and Martin Michel discuss the possible existence of additional NPY receptor subtypes with Y5-like recognition features and their presence in peripheral tissues [6].
• The coupling of NPY receptors to various signal transduction mechanisms is also reviewed, including inhibition of adenylyl cyclase and stimulation or inhibition of increases in intracellular Ca2+, but a link between individual NPY receptor subtypes and specific signal transduction pathways has not been established [7].
• Here we report the cloning by expression of a novel NPY receptor subtype from a rat hypothalamus cDNA library [8].
• Expression of pS2, neuropeptide Y receptor Y1 and three novel clones was induced by estradiol, indicating estrogen-responsiveness [9].
• The expression of the neuropeptide Y receptor Y1 gene (NPY1R localized at 4q31.3-q32) and the human guanine nucleotide-binding regulatory protein Go-alpha (GNAO1 localized at 16q13) was significantly decreased in individuals with schizophrenia compared to unaffected family controls by microarray and real-time PCR [10].

Biological context of NPY1R

• As in the type 1 NPY receptor (Y1 receptor) gene, the 5'-untranslated region of the Y2 receptor is interrupted by an intervening sequence ( approximately 4.5 kb) [11].
• To further our understanding of the genetic elements involved in the regulation of NPY receptor expression, we have cloned and characterized the human gene encoding the type 2 NPY receptor (Y2 receptor, HGMW-approved symbol NPY2R).2 The transcript spans 9 kb of genomic sequence and is encoded on two exons [11].
• Specific links between individual NPY receptor subtype and a particular signal transduction pathway are not established [12].
• Current drug discovery has produced a number of highly selective NPY receptor antagonists which have been used to establish the NPY Y(1) receptor subtype as the most critical in regulating short-term food intake [13].
• However, it is too early to state with certainty whether a single subtype selective drug used alone or a combination of NPY receptor selective antagonists used in combination will be necessary to adequately influence appetite regulation [13].

Anatomical context of NPY1R

• NPY receptor subtype in the rabbit isolated ileum [14].
• The reduction of NPY-receptor-mediated responses with age may influence sympathetic nervous system control of the venous system with advancing age [15].
• We conclude that from four known NPY receptor subtypes in the rat (Y(1), Y(2), Y(4), Y(5)), only the NPY Y(1) receptor can be linked to anxiety-regulation with certainty in the forebrain, and that NPY Y(2) receptor may have a role in the pons [16].
• Microinjection studies with NPY and NPY receptor antagonists support the hypothesis that the amygdala, the dorsal periaqueductal gray matter, dorsocaudal lateral septum and locus coeruleus form a neuroanatomical substrate that mediates anxiolytic-like effects of NPY [16].
• alpha(2)-adrenoceptor and NPY receptor-mediated contractions of porcine isolated blood vessels: evidence for involvement of the vascular endothelium [17].

Associations of NPY1R with chemical compounds

• Altered expression of NPY1R and C3 was also demonstrated at the protein level [18].
• It is concluded that NPY releases intracellular Ca2+ from an inositol 1,4,5-trisphosphate-sensitive calcium pool, which is restored by external calcium, and that NPY receptor desensitization is protein kinase C independent [19].
• CONCLUSIONS: Blockade of the NPY receptor may produce appetite-suppressing drugs [13].
• ATP (10 micromol/l), a stable analogue ADP-beta S (3 micromol/l), and NE (1 micromol/l) had no effect on acetylcholine release. m-RNA for the NPY-receptor subtypes Y(1), Y(2), Y(4), Y(5), and y(6) was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) [20].
• Our results demonstrate that (1) NPY modulates microvascular hemodynamics by changes in arteriolar diameter, (2) the NPY receptor on the hamster cheek pouch microvasculature is of the Y1 type, and (3) exogenous NPY-induced vasoconstriction is independent of the activity of endogenous norepinephrine [21].

Physical interactions of NPY1R

• The regulation of NPY/NPY-R expression and function appears to be part of a complex system controlling multiple physiological functions, and its disruption might be relevant in the pathophysiology of disease states such as obesity [22].

Other interactions of NPY1R

• Neuropeptide Y and its receptors NPY1R and NPY5R play a role in hippocampal learning and memory [23].
• Novel treatments may emerge based upon VIP and NPY receptor antagonists if further work substantiates a role for gp120 in the vascular abnormalities of AIDS [24].
• These values were compared to their binding affinities (IC50) for rat NPY receptor subtypes Y1, Y2, Y4 and Y5 in vitro [25].
• Therefore, in the present study we investigated whether the anxiolytic action of (2S,3S,4S)-(carboxycyclopropyl)glycine (L-CCG-I), an mGlu2/3 receptor agonist, and (1S,3R,4S)-1-aminocyclopentane-1,3,4-tricarboxylic acid (ACPT-1), an mGluR4/6/7/8 receptor agonist, was mediated by a mechanism involving NPY receptor [26].
• SNP, SIN-1, and SNAP decreased normal binding of NPY to the NPY1 receptor in SK-N-MC cells in a concentration-dependent manner [27].

Analytical, diagnostic and therapeutic context of NPY1R

• We report here the molecular cloning of a cDNA sequence encoding a human NPY receptor and the corrected sequence for a rat homologue [28].
• Quantitative western blot analyses confirmed decreased expression of NPY1R in all eight MTLE patients tested [18].
• We have engineered an immortalized amygdalar cell line (AR-5 cells) which express via RT-PCR, the CRF(2alpha), Y(1) and Y(5) NPY receptor [29].
• Re-evaluation of receptor-ligand interactions of the human neuropeptide Y receptor Y1: a site-directed mutagenesis study [30].

References