Activation of prostaglandin E receptor EP4 subtype suppresses food intake in mice
Activation of prostaglandin E receptor EP4 subtype suppresses food intake in mice
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DOI：
10.1016/j.prostaglandins.2006.06.008
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发表时间：
2006-10-01
影响因子：
2.9
通讯作者：
Yoshikawa, Masaaki
中科院分区：
文献类型：
--
作者：
Ohinata, Kousaku;Suetsugu, Kentaro;Yoshikawa, Masaaki
前列腺素（PG）E-2是一种在各种哺乳动物大脑中产生的生物活性脂质，在中枢给药后减少食物摄入。我们使用高选择性配体检测了PGE（2）受体的四种不同亚型（EP 1-EP 4）中的哪一种介导了PGE（2）的促凋亡作用。PGE（2）0.1-10 nmol/只可减少侧脑室注射（i. c. v.）在禁食小鼠中以剂量依赖性方式施用。以1-10 nmol/小鼠的剂量集中给药EP 4激动剂ONO-AE 1 -329模拟PGE的促凋亡作用（2）。EP 4拮抗剂ONO-AE 3 -208以10 nmol/只的剂量改善PGE（2）或EP 4激动剂的促凋亡作用。因此，中枢神经系统中PGE（2）-EP 4信号的激活抑制了食物摄入。剂量为10 nmol/小鼠的EP 4激动剂延迟胃排空和血糖升高。(c)2006爱思唯尔公司All rights reserved.
Prostaglandin (PG) E-2, a bioactive lipid produced in the brains of various mammals, decreases food intake after central administration. We examined which of four distinct subtypes of PGE(2) receptors (EP1-EP4) mediated the anorexigenic action of PGE(2) using highly selective ligands. PGE(2) at a dose of 0.1-10 nmol/mouse decreased food intake after intracerebroventricular (i.c.v.) administration in a dose-dependent manner in fasted mice. A centrally administered EP4 agonist, ONO-AE1-329 at a dose of 1-10 nmol/mouse mimicked the anorexigenic action by PGE(2). The anorexigenic action of PGE(2) or EP4 agonist was ameliorated by EP4 antagonist ONO-AE3-208 at a dose of 10 nmol/mouse. Thus, activation of PGE(2)-EP4 signaling in the central nervous system suppresses food intake. The EP4 agonist at a dose of 10 nmol/mouse delayed gastric emptying and elevated blood glucose. (c) 2006 Elsevier Inc. All rights reserved.