RGD Reference Report - Neuropeptide Y suppresses absence seizures in a genetic rat model primarily through effects on Y receptors. - Rat Genome Database

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Neuropeptide Y suppresses absence seizures in a genetic rat model primarily through effects on Y receptors.

Authors: Morris, MJ  Gannan, E  Stroud, LM  Beck-Sickinger, AG  O'Brien, TJ 
Citation: Morris MJ, etal., Eur J Neurosci. 2007 Feb;25(4):1136-43.
RGD ID: 10448963
Pubmed: PMID:17331209   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1460-9568.2007.05348.x   (Journal Full-text)

Neuropeptide Y (NPY) potently suppresses absence seizures in a model of genetic generalized epilepsy, genetic absence epilepsy rats of Strasbourg (GAERS). Here we investigated the Y-receptor subtype(s) on which NPY exerts this anti-absence effect. A dual in vivo approach was used: the cumulative duration of seizures was quantified in adult male GAERS in 90-min electroencephalogram recordings following intracerebroventricular (i.c.v.) injection of: (i) subtype-selective agonists of Y1 ([Leu31Pro34]NPY, 2.5 nmol), Y2 (Ac[Leu(28,31)]NPY24-36, 3 nmol), Y5 receptors [hPP1(-17),Ala31,Aib32]NPY, 4 nmol), NPY (3 nmol) or vehicle; and following (ii) i.c.v. injection of antagonists of Y1 (BIBP3226, 20 nmol), Y2 (BIIE0246, 20 nmol) and Y5 (NPY5RA972, 20 nmol) receptors or vehicle, followed by NPY (3 nmol). Injection of the Y1- and Y5-selective agonists resulted in significantly less mean seizure suppression (37.4% and 53.9%, respectively) than NPY (83.2%; P < 0.05), while the Y2 agonist had similar effects to NPY (62.3% suppression, P = 0.57). Food intake was not increased following injection of the Y2 agonist, while significant increases in food intake were seen following NPY and the other Y-subtype agonists. Compared with vehicle, NPY injection suppressed seizures following the Y1 and Y5 antagonists (45.3% and 80.1%, respectively, P < 0.05), but not following the Y2 antagonist (5.1% suppression, P = 0.46). We conclude that NPY Y2 receptors are more important than Y1 and Y5 receptors in mediating the effect of NPY to suppress absence seizures in a genetic rat model. Y2 receptor agonists may represent targets for novel drugs against genetic generalized epilepsies without resulting in appetite stimulation.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  

Objects Annotated

Genes (Rattus norvegicus)
Npy  (neuropeptide Y)
Npy1r  (neuropeptide Y receptor Y1)
Npy2r  (neuropeptide Y receptor Y2)
Npy5r  (neuropeptide Y receptor Y5)

Genes (Mus musculus)
Npy  (neuropeptide Y)
Npy1r  (neuropeptide Y receptor Y1)
Npy2r  (neuropeptide Y receptor Y2)
Npy5r  (neuropeptide Y receptor Y5)

Genes (Homo sapiens)
NPY  (neuropeptide Y)
NPY1R  (neuropeptide Y receptor Y1)
NPY2R  (neuropeptide Y receptor Y2)
NPY5R  (neuropeptide Y receptor Y5)


Additional Information