Role for central ghrelin in food intake and secretion profile of stomach ghrelin in rats
Role for central ghrelin in food intake and secretion profile of stomach ghrelin in rats
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DOI：
10.1677/joe.0.1740283
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发表时间：
2002-08-01
影响因子：
4
通讯作者：
Kangawa, K
中科院分区：
文献类型：
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作者：
Murakami, N;Hayashida, T;Kangawa, K
Ghrelin是一种28-氨基酸肽，最近从大鼠胃中分离出，作为GH促分泌素受体的内源性配体。我们以前曾报道，中枢或外周给药的生长激素释放肽刺激大鼠的食物摄入，生长激素和胃酸的分泌。在本研究中，我们调查了多少内源性中枢释放的ghrelin参与控制食物摄入和体重增加。我们还使用两种抗生长素释放肽抗血清，一种针对肽的N-末端（[Cys（12）]-生长素释放肽[1-11]）区域，另一种针对肽的C-末端（[Cyso]-生长素释放肽[13-28]）区域，通过RIA检查了生长素释放肽从胃中分泌的概况。前一种抗体特异性识别具有正辛酰化Ser（3）的生长素释放肽（酰基生长素释放肽），并且不识别脱酰基生长素释放肽。后者还识别脱酰基生长素释放肽（即总生长素释放肽）。脑室内治疗的抗生长素释放肽抗血清对N-末端区域，每天两次，共5天，每天的食物摄入量和体重显着下降。去酰基ghrelin水平显着高于在胃静脉比在躯干。无论是禁食12小时，胃泌素或胆囊收缩素的管理导致增加的酰基和脱酰基ghrelin水平。生长激素释放肽水平表现出昼夜模式，双峰峰出现在黑暗和光明的时期。这两个峰分别与胃内容物的最大和最小体积一致。这些结果表明：（1）内源性中枢释放的ghrelin参与调节食物摄入和体重，（2）酰基ghrelin从胃分泌，（3）肠激素刺激ghrelin从胃释放，和（4）ghrelin的昼夜节律的调节是复杂的，因为ghrelin分泌在胃排空和充盈的条件下都增加。
Ghrelin, a 28-ammo-acid peptide, has recently been isolated from the rat stomach as an endogenous ligand for the GH secretagogue receptor. We have reported previously that central or peripheral administration of ghrelin stimulates food intake, and the secretion of GH and gastric acid in rats. In the present study, we investigated how much endogenous centrally released ghrelin is involved in the control of food intake and body weight gain. We also examined the profile of ghrelin secretion from the stomach by RIA using two kinds of anti-ghrelin antiserum, one raised against the N-terminal ([Cys(12)]-ghrelin[1-11]) region and one raised against the C-terminal ([Cyso]-ghrelin [13-28]) region of the peptide. The former antibody recognizes specifically ghrelin with n-octanoylated Ser(3) (acyl ghrelin), and does not recognize des-acyl ghrelin. The latter also recognizes des-acyl ghrelin (i.e. total ghrelin). Intracerebroventricular treatment with the antighrelin antiserum against the N-terminal region twice a day for 5 days decreased significantly both daily food intake and body weight. Des-acyl ghrelin levels were significantly higher in the gastric vein than in the trunk. Either fasting for 12 h, administration of gastrin or cholecystokinin resulted in increase of both acyl and des-acyl ghrelin levels. The ghrelin levels exhibited a diurnal pattern, with the bimodal peaks occurring before dark and light periods. These two peaks were consistent with maximum and minimum volumes of gastric content respectively. These results suggest that (1) endogenous centrally released ghrelin participates in the regulation of food intake and body weight, (2) acyl ghrelin is secreted from the stomach, (3) intestinal hormones stimulate ghrelin release from the stomach, and (4) regulation of the diurnal rhythm of ghrelin is complex, since ghrelin secretion is augmented under conditions of both gastric emptying and filling.