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用新型双重食欲素受体拮抗剂预处理对大鼠胃饥饿素诱导的进食的抑制作用。

Inhibition of ghrelin-induced feeding in rats by pretreatment with a novel dual orexin receptor antagonist.

作者信息

So Mariko, Hashimoto Hirofumi, Saito Reiko, Yamamoto Yukiyo, Motojima Yasuhito, Ueno Hiromichi, Sonoda Satomi, Yoshimura Mitsuhiro, Maruyama Takashi, Kusuhara Koichi, Ueta Yoichi

机构信息

Department of Health and Nutritional Care, Faculty of Medical Science, University of East Asia, Shimonoseki, 751-0807, Japan.

Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.

出版信息

J Physiol Sci. 2018 Mar;68(2):129-136. doi: 10.1007/s12576-016-0517-5. Epub 2017 Jan 4.

DOI:10.1007/s12576-016-0517-5
PMID:28054308
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6394659/
Abstract

Orexin-A and -B, and ghrelin are potent orexigenic peptides. The effects of ACT462206, a novel dual orexin receptor antagonist (DORA), on ghrelin-induced feeding were examined in adult male Wistar rats. Hyperphagia induced by the intracerebroventricular (icv) administration of ghrelin was significantly suppressed for at least 2 h by pretreatment with icv administration of DORA. A marked increase was observed in the number of neurons showing Fos immunoreactivity in the paraventricular nucleus, arcuate nucleus and lateral hypothalamic area (LHA), 90 min after icv administration of ghrelin. Pretreatment with DORA significantly decreased the number of Fos-immunoreactive (IR) neurons; however, Fos immunoreactivity remained significantly increased. Double-immunostaining for Fos and orexin-A showed that many orexin-A-IR neurons in the LHA coexisted with Fos immunoreactivity after icv administration of ghrelin, but their number was reduced significantly by DORA pretreatment. These results suggest that centrally administered ghrelin may activate the orexinergic and non-orexinergic pathways responsible for the regulation of feeding.

摘要

食欲素A和B以及胃饥饿素都是强效的促食欲肽。在成年雄性Wistar大鼠中研究了新型双食欲素受体拮抗剂（DORA）ACT462206对胃饥饿素诱导进食的影响。脑室注射胃饥饿素诱导的食欲亢进，经脑室注射DORA预处理后至少2小时得到显著抑制。脑室注射胃饥饿素90分钟后，在室旁核、弓状核和下丘脑外侧区（LHA）观察到Fos免疫反应阳性神经元数量显著增加。DORA预处理显著减少了Fos免疫反应阳性（IR）神经元的数量；然而，Fos免疫反应性仍显著增加。Fos和食欲素A的双重免疫染色显示，脑室注射胃饥饿素后，LHA中许多食欲素A-IR神经元与Fos免疫反应性共存，但DORA预处理使其数量显著减少。这些结果表明，中枢给予胃饥饿素可能激活负责调节进食的食欲素能和非食欲素能途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f32/10717572/c44f581cc7fc/12576_2016_517_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f32/10717572/8e3cf415a0d3/12576_2016_517_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f32/10717572/dcf3eafc5899/12576_2016_517_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f32/10717572/afbc541e7f03/12576_2016_517_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f32/10717572/c44f581cc7fc/12576_2016_517_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f32/10717572/8e3cf415a0d3/12576_2016_517_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f32/10717572/dcf3eafc5899/12576_2016_517_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f32/10717572/afbc541e7f03/12576_2016_517_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f32/10717572/c44f581cc7fc/12576_2016_517_Fig4_HTML.jpg

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