Korczynski W, Ceregrzyn M, Matyjek R, Kato I, Kuwahara A, Wolinski J, Zabielski R
The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Science, Jablonna, Poland.
J Physiol Pharmacol. 2006 Nov;57 Suppl 6:17-42.
Orexin-A (OXA, hypocretin-1) and orexin-B (OXB, hypocretin-2) are peptides derived from the same 130 amino acid long precursor (prepro-orexin) that bind and activate two closely related orphan G protein-coupled receptors. Orexins and their receptors were first discovered in the rat brain, and soon after that in peripheral neural structures, including the vagal nerve and enteric nervous system, and in other structures involving the gastrointestinal tract diffuse neuroendocrine system, pancreas tissue, stomach and intestinal mucosa. Orexins and their receptors were also demonstrated in the testes, adrenals, kidneys, and placenta. This review is focused on central and enteric actions. Originally, orexins were considered to be neurotransmitters that centrally stimulate food intake in animals and humans, but it soon became evident that their action is broader due to activation of a large number of neuronal pathways involved in energy homeostasis, sleep-awake behavior, nociception reward seeking, food and drug addiction, as well as reproduction, cardiovascular and adrenal function. In the gastrointestinal tract, orexins have been found so far to affect gastrointestinal motility and gastric, intestinal and pancreatic secretions. The effects were observed following central (intraventricular) or local (intraluminal, intraarterial), but not peripheral (intravenous), administrations of orexins. Since the expression of orexins in the gastrointestinal tract is enhanced during fasting, and fasting reveals many of the orexin gastrointestinal effects, it seems probable that on the local level, orexins keep the gastrointestinal tract functions ready during fasting and play role in brain-gut axis control.
食欲素A(OXA,下丘脑泌素-1)和食欲素B(OXB,下丘脑泌素-2)是源自同一130个氨基酸长的前体(前食欲素原)的肽,它们结合并激活两个密切相关的孤儿G蛋白偶联受体。食欲素及其受体最初在大鼠脑中被发现,此后不久在包括迷走神经和肠神经系统在内的外周神经结构以及涉及胃肠道弥漫性神经内分泌系统、胰腺组织、胃和肠黏膜的其他结构中也被发现。在睾丸、肾上腺、肾脏和胎盘中也证实了食欲素及其受体的存在。本综述聚焦于中枢和肠道作用。最初,食欲素被认为是在中枢刺激动物和人类食物摄入的神经递质,但很快就发现它们的作用更为广泛,因为它们激活了大量参与能量稳态、睡眠-觉醒行为、伤害感受性奖赏寻求、食物和药物成瘾以及生殖功能、心血管和肾上腺功能的神经通路。在胃肠道中,到目前为止已发现食欲素会影响胃肠蠕动以及胃、肠和胰腺的分泌。这些作用是在中枢(脑室内)或局部(腔内、动脉内)而非外周(静脉内)给予食欲素后观察到的。由于禁食期间胃肠道中食欲素的表达会增强,且禁食揭示了食欲素的许多胃肠道作用,因此在局部水平上,食欲素似乎在禁食期间使胃肠道功能保持就绪状态,并在脑-肠轴控制中发挥作用。