Leilei Pan,Shuifeng Xiao,Zichao Xu,Wenping Li,Long Zhao,Ling Zhang,Ruirui Qi,Junqin Wang,Yiling Cai
Background and Purpose We evaluated the hypothesis that central orexin application could counteract motion sickness responses through regulating neural activity in target brain areas. Experimental Approach Thec effects of intracerebroventricular (i.c.v.) injection of orexin-A and SB-334867 (OX 1 antagonist) on motion sickness-induced anorexia, nausea-like behaviour (conditioned gaping), hypoactivity and hypothermia were investigated in rats subjected to Ferris wheel-like rotation. Orexin-A responsive brain areas were identified using Fos immunolabelling and were verified via motion sickness responses after intranucleus injection of orexin-A, SB-334867 and TCS-OX2-29 (OX 2 antagonist). The efficacy of intranasal application of orexin-A versus scopolamine on motion sickness symptoms in cats was also investigated. Key Results Orexin-A (i.c.v.) dose-dependently attenuated motion sickness-related behavioural responses and hypothermia. Fos expression was inhibited in the ventral part of the dorsomedial hypothalamus (DMV) and the paraventricular nucleus (PVN), but was enhanced in the ventral part of the premammillary nucleus ventral part (PMV) by orexin-A (20 μg) in rotated animals. Motion sickness responses were differentially inhibited by orexin-A injection into the DMV (anorexia and hypoactivity), the PVN (conditioned gaping) and the PMV (hypothermia). SB-334867 and TCS-OX2-29 (i.c.v. and intranucleus injection) inhibited behavioural and thermal effects of orexin-A. Orexin-A (60 μg·kg −1 ) and scopolamine inhibited rotation-induced emesis and non-retching/vomiting symptoms, while orexin-A also attenuated anorexia with mild salivation in motion sickness cats. Conclusion and Implications Orexin-A might relieve motion sickness through acting on OX 1 and OX 2 receptors in various hypothalamus nuclei. Intranasal orexin-A could be a potential strategy against motion sickness.
Liping Yang,Shaoyang Zhi,Junyi Hu,Wenlei Zhang,Yuru Zhang,Chaobin Qin,Guokun Yang,Xiao Yan,Guoxing Nie
Orexins are neuropeptides involved in energy homeostasis. In fish, the function of orexin-A in glucose metabolism is less reported. The present study aims to identify the potential role of orexin-A in the glucose absorption and metabolism in common carp. The full length of orexin cDNA was cloned using RT-PCR and RACE method. The prepro-orexin cDNA was 513 bp containing an open reading frame of 474 bp and encoded 157 amino acids which including 47 amino acids of orexin-A and 28 amino acids of orexin-B. The tissue distribution results showed that orexin was expressed in multiple tissues, especially with high-level expression in hypothalamus. The exogenous orexin-A protein was chemical synthesized. Intraperitoneal injection of orexin-A alleviated the increase of plasma glucose level at 1 h and 2 h after OGTT (Oral glucose tolerance test). Orexin-A also decreased glucose uptake activity and the expression of sglt1 and glut2 mRNA in intestine. However, orexin-A significantly increased the mRNA expression of glut2 in liver and glut4 in muscle. Moreover, the gluconeogenesis-related gene fbpase mRNA was significantly down-regulated, while glycolysis-related genes gk and hk were significantly up-regulated after treatment with orexin-A in vivo and vitro. These results implied that hyperglycemia could be alleviated in common carp after the injection of orexin-A and suggest a role of this peptide as a plasma glucose regulator by inhibition glucose absorption in intestine, promotion glucose transport to liver and muscle. Furthermore, hepatic gluconeogenesis was inhibited. Taken together, this study helped to understand the characterization of prepro-orexin and the function of orexin-A in fish glucose homeostasis.
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