Disease relevance of Npy5r

• Chronic neuropeptide Y infusion into the lateral ventricle induces sustained feeding and obesity in mice lacking either Npy1r or Npy5r expression [1].
• To further investigate the importance of these two receptors in NPY-induced hyperphagia after chronic central administration, we used mice lacking either Npy1r or Npy5r expression [1].
• The compound did not affect the body weight of lean mice fed a regular diet or genetically obese leptin receptor-deficient mice or rats, despite similarly high brain Y5R receptor occupancy [2].

Psychiatry related information on Npy5r

• For this reason, NPY-Y5 receptor antagonists may be useful in medical management of alcohol abuse and alcoholism [3].

High impact information on Npy5r

• We have inactivated the Y5R gene in mice and report that younger Y5R-null mice feed and grow normally; however, they develop mild late-onset obesity characterized by increased body weight, food intake and adiposity [4].
• Exogenous NPY at physiological concentrations also induces Y5 receptor, stimulates neovascularization, and restores ischemic muscle blood flow and performance [5].
• The data demonstrate that the NPY Y5 receptor subtype plays a role in NPY-induced food intake, but also suggest that, with chronic blockade, counterregulatory mechanisms are induced to restore appetite [6].
• The Y5R antagonist selectively ameliorated diet-induced obesity (DIO) in rodents by suppressing body weight gain and adiposity while improving the DIO-associated hyperinsulinemia [2].
• These data demonstrate that Y5R has an important role in mediating NPY's inhibitory actions in the mouse hippocampus and suggest a role for Y5R in the control of limbic seizures [7].

Biological context of Npy5r

• Our comparisons strongly suggest that the tight cluster of NPY1R, NPY2R, and NPY5R on human chromosome 4 (HSA4) represents the ancestral configuration, whereas the porcine cluster has been split by two inversions on SSC8 [8].
• Taken together, these data strongly suggest biological redundancies between Y1 and Y5 receptor signaling in the NPY-mediated control of food intake [1].
• The mouse NPY-Y5 receptor gene consists of at least two exons with a 7.0 kbp-long intronic sequence and is localized in the chromosome 8B3-C2 region [9].
• In contrast, NPYergic inhibition of excitatory CA3 synaptic transmission is absent in mice lacking the Y5R subtype (Y5R KO) [10].
• Therefore, the Y5 receptor can play a key role in regulating energy homeostasis [11].

Anatomical context of Npy5r

• Northern blot analysis indicated that the mouse NPY-Y5 receptor mRNA was highly expressed in the brain, but not in the heart, kidney, spleen, lung, liver, skeletal muscle, and testis [9].
• Characterization of neuropeptide Y Y2 and Y5 receptor expression in the mouse hypothalamus [12].
• In contrast, Y5 receptor expression appears to be restricted to epithelial crypts of the small intestine and nonepithelial tissue of colon [13].
• There were minor changes in the amount of Y5 receptor mRNA expression in the hippocampal formation and medial habenular nucleus [14].
• Northern blot analysis reveals that the Y5 receptor is widely distributed in the human brain, with the strongest signals detected in the cortex, putamen and caudate nucleus [15].

Associations of Npy5r with chemical compounds

• CONCLUSIONS: These results indicate that blockade NPY Y5 receptor activity modulates the onset and maintenance of ethanol self-administration [3].
• METHODS: Effects of the novel NPY Y5 receptor antagonist L-152,804 on the onset and maintenance of operant self-administration were examined in male C57BL/6J mice, which were trained to self-administer ethanol (10% v/v) versus water via the sucrose substitution method during 16 hr overnight sessions [3].
• We report that Y5R-/- mice do not exhibit spontaneous seizure-like activity; however, they are more sensitive to kainic acid-induced seizures [7].

Other interactions of Npy5r

• We therefore investigated the central effects of porcine NPY, selective Y1, Y2 and Y5 receptor agonists and a Y1 receptor antagonist on heart rate (HR) and HR variability in freely moving mice using auditory fear conditioning [16].
• DISCUSSION: Central activation of both Y1 and Y5 receptors increases RQ and adiposity, whereas only Y5 receptor activation reduces energy expended per energy ingested [17].
• Significant decreases in Y5 receptor mRNA expression were found in the ventromedial, dorsomedial and arcuate hypothalamic nuclei, midline thalamic nuclei, piriform, cingulate and retrosplenial granular cortices of the obese mouse brain [14].
• Y5 receptor knockout (Y5 -/-) mice on an inbred 129/SvEv background showed normal ethanol-induced locomotor activity and normal voluntary ethanol consumption, but displayed increased sleep time caused by 2.5 and 3.0 g/kg injection of ethanol [18].

Analytical, diagnostic and therapeutic context of Npy5r

• To determine whether deletion of individual Y-receptors results in altered mRNA expression and/or binding toward other Y-receptor types, we applied in-situ hybridization and radioligand-binding studies on brain slices of Npy1r-, Npy2r- or Npy5r-knockout mice [19].
• Molecular cloning, organization and localization of the gene for the mouse neuropeptide Y-Y5 receptor [9].
• Oral administration of a selective Y5 antagonist at a dose of 100 mg/kg twice a day completely suppressed all of these D-Trp(34)NPY-induced changes, indicating that chronic activation of the Y5 receptor produces hyperphagia and obesity [11].

References