Inhibition of ghrelin-induced feeding in rats by pretreatment with a novel dual orexin receptor antagonist |
| |
| Authors: | Mariko So Hirofumi Hashimoto Reiko Saito Yukiyo Yamamoto Yasuhito Motojima Hiromichi Ueno Satomi Sonoda Mitsuhiro Yoshimura Takashi Maruyama Koichi Kusuhara Yoichi Ueta |
| |
| Affiliation: | 1.Department of Health and Nutritional Care, Faculty of Medical Science,University of East Asia,Shimonoseki,Japan;2.Department of Physiology, School of Medicine,University of Occupational and Environmental Health,Kitakyushu,Japan;3.Department of Pediatrics, School of Medicine,University of Occupational and Environmental Health,Kitakyushu,Japan |
| |
| 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. |
| |
| Keywords: | |
| 本文献已被 SpringerLink 等数据库收录！ |
|
