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Inhibition of food intake by neuropeptide Y Y5 receptor antisense oligodeoxynucleotides

Schaffhauser, A. O. and Stricker-Krongrad, A. and Brunner, L. and Cumin, F. and Gerald, C. and Whitebread, S. and Criscione, L. and Hofbauer, K. G.. (1997) Inhibition of food intake by neuropeptide Y Y5 receptor antisense oligodeoxynucleotides. Diabetes, Vol. 46, H. 11. pp. 1792-1798.

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Official URL: http://edoc.unibas.ch/dok/A5258622

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Abstract

The recently discovered rat neuropeptide Y (NPY) receptor, the Y5 subtype, has been proposed to mediate the NPY-induced feeding response and therefore plays a central role in the regulation of food intake. These conclusions were based on studies with peptidic agonists. We now report studies in which phosphothioate end-protected antisense oligodeoxynucleotides (ODNs) targeted to prepro NPY (prepro NPY antisense ODNs) or to the Y5 receptor (Y5 antisense ODNs) were used to assess the functional importance of this novel receptor subtype in vivo. NPY antisense ODNs given intracerebroventricularly to rats prevented the increase in hypothalamic NPY levels during food deprivation and inhibited fasting-induced food intake. Likewise, repeated intracerebroventricular injections of Y5 antisense ODNs prevented fasting-induced food intake in rats. Moreover, two Y5 antisense ODNs, targeted to different sequences of the receptor, significantly decreased basal food intake and inhibited the increase in food intake after intracerebroventricular injection of NPY. These effects proved to be selective, since the feeding response to galanin was not affected. Analysis of the structure of feeding behavior revealed that prepro NPY and Y5 receptor antisense ODNs reduced food intake by inducing decreases in meal size and meal duration analogous to the orexigenic effects of NPY that are mediated by increases in these parameters. Although changes in Y5 receptor density could not be measured, the results with Y5 antisense ODNs strongly suggest that this receptor subtype mediates the feeding response to exogenous and endogenous NPY. Selective Y5 antagonists may therefore be of therapeutic value for the treatment of obesity and eating disorders.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Pharmacology/Neurobiology (Hofbauer)
UniBasel Contributors:Hofbauer, Karl G.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Diabetes Association
ISSN:0012-1797
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:22 Mar 2012 14:20
Deposited On:22 Mar 2012 13:20

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