{"id":505,"date":"2018-08-31T01:59:44","date_gmt":"2018-08-31T06:59:44","guid":{"rendered":"http:\/\/www.creative-peptides.com\/blog\/?p=505"},"modified":"2018-08-31T02:00:52","modified_gmt":"2018-08-31T07:00:52","slug":"agonists-and-antagonists-for-npy-family-receptors","status":"publish","type":"post","link":"https:\/\/www.creative-peptides.com\/blog\/agonists-and-antagonists-for-npy-family-receptors\/","title":{"rendered":"Agonists and antagonists for NPY-family receptors"},"content":{"rendered":"

Peptide ligands<\/p>\n

Over the past four years there\u2019s been considerable progress in the development of\u00a0novel selective analogs of NPY<\/a>. A number of these analogs have been directed\u00a0toward discovering tools to understand the role of the Y1 and Y5 receptors in the\u00a0feeding produced by central administration of NPY. For instance, several novel\u00a0analogs of NPY have been found to be highly selective for the Y1 receptor. These all produce an increase in feeding after intracerebroventricular administration. Over 4h, [D-Arg25<\/sup>]-NPY produced\u00a0a similar increase in feeding compared to NPY. This increase in feeding was blocked\u00a0by the peptidic Y1 antagonist 1229U91. However, it was found that 1229U91,\u00a0besides being a Y1 antagonist, also is a potent\u00a0agonist at the Y4 receptor.\u00a0Soll and co-workers have reported a very potent and Y1 selective peptide\u00a0[Phe7<\/sup>, Pro34<\/sup>]-NPY, though no work has been reported on its effects in vivo. In addition to novel Y1 receptor agonists, an analog of the Y1 selective peptide antagonist\u00a01229U91 was recently reported. This analog consisted of an OMe replacement for the amide in 1229U91 (GR231118). This peptide retained high affinity for\u00a0the Y1 receptor but had much reduced affinity for the Y4 receptor when compared\u00a0to 1229U91. In functional assays, this peptide analog potently antagonized the NPY\u00a0inhibition of forskolin-stimulated adenylate cyclase in Y1 receptor containing cells\u00a0while having no effect (agonist or antagonist) in Y4 receptor containing cells. When\u00a0administered intrahypothalamically, this Y1 antagonist inhibited both NPY stimulated\u00a0feeding as well as feeding in schedule fed rats.<\/p>\n

More limited work has been performed to obtain Y2 selective peptide analogs.\u00a0One of the more promising peptide analogs was recently published by Soll et al. This peptide (Cyclo S-S [Cys20<\/sup>, Cys24<\/sup>]pNPY) exhibits subnanomolar affinity\u00a0for the Y2 receptor with low micromolar affinity at Y1 and Y5. No additional information is available in the scientific literature that further describes the properties of\u00a0this compound. On the other hand, considerable progress has been made for developing Y5 selective agonists. However, several of these peptide analogs have considerable affinity for both the Y4 and Y5 receptors. One of these analogs, 2-36[K4, RYYSA19-23<\/sup>]-PP, produced a dose-dependent increase in food consumption\u00a0after intracerebroventricular administration. The magnitude of this increase in\u00a0food intake exceeded that produced by identical doses of NPY. More selective Y5\u00a0agonist peptides have also been reported that have little affinity for the Y4 receptor.\u00a0One of these, [Ala31<\/b><\/sup><\/strong>, Aib32<\/sup>]-NPY was found to produce a small increase in food\u00a0intake when compared to control animals. Another analog, [cPP1-7<\/sup>, NPY19-23<\/sup>,\u00a0Ala31<\/sup>, Aib32<\/sup>, Gln34<\/sup>]-hPP, which exhibited an approximately 20-fold higher affinity\u00a0for the Y5 receptor when compared to analog [Ala31<\/sup>, Aib32<\/sup>]-NPY, produced increases in food intake that exceeded NPY at similar doses. Finally, the relatively low affinity analog, p[D-Trp34<\/sup>]-NPY, was reported to be a selective Y5 agonist. This peptide produced a similar inhibition of forskolin-stimulated adenylate\u00a0cyclase to that seen for NPY and was found to increase food intake after intracerebroventricular administration. However, the increase was not as substantial is that\u00a0observed with similar doses of NPY. The putative Y5 selective antagonist,\u00a0CGP71683A, antagonized the increase in food intake produced by this peptide,\u00a0however, the specificity of CGP71683A has recently been called into question.<\/p>\n

Reference<\/h4>\n

Zukowska, Z., & Feuerstein, G. Z. (Eds.). (2006). The NPY Family of Peptides in Immune Disorders, Inflammation, Angiogenesis, and Cancer. Springer Science & Business Media.<\/p>\n","protected":false},"excerpt":{"rendered":"

Peptide ligands Over the past four years there\u2019s been considerable progress in the development of\u00a0novel selective analogs of NPY. A number of these analogs have been directed\u00a0toward discovering tools to …<\/p>\n","protected":false},"author":1,"featured_media":506,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[75],"tags":[],"_links":{"self":[{"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/posts\/505"}],"collection":[{"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/comments?post=505"}],"version-history":[{"count":2,"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/posts\/505\/revisions"}],"predecessor-version":[{"id":508,"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/posts\/505\/revisions\/508"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/media\/506"}],"wp:attachment":[{"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/media?parent=505"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/categories?post=505"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/tags?post=505"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}