Hindbrain GRP receptor blockade antagonizes feeding suppression by peripherally administered GRP
Hindbrain GRP receptor blockade antagonizes feeding suppression by peripherally administered GRP
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DOI：
10.1152/ajpregu.1996.271.1.r180
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发表时间：
1996-07-01
影响因子：
2.8
通讯作者：
Moran, TH
中科院分区：
文献类型：
--
作者：
Ladenheim, EE;Taylor, JE;Moran, TH
外周或中枢注射Bombesin （BN）样肽抑制大鼠的食物摄入。BN的中枢和外周作用之间的关系尚不清楚。然而，实验证据支持尾侧后脑在介导BN摄食效应中起关键作用。为了进一步研究这种关系，我们检测了第四心室输注特定胃泌素释放肽（GRP）拮抗剂的能力；[D-F-5,Phe(6),D-Ala(11)]BN-(6-13)甲酯（BN- me），阻断GRP-(18-27)腹腔注射5 h无食雄性Sprague-Dawley大鼠（n = 10）对葡萄糖摄入（0.5 kcal/ml）的抑制。我们发现，第四心室给药10、32和100 ng BN-ME阻断了外周给药10 nmol/kg GRP-对葡萄糖摄入的抑制（18-27）。BN-ME的最有效剂量（100 ng）阻断了外周注射GRP-(18-27)抑制葡萄糖摄入的能力，但单独给药时对摄入没有影响。这些结果表明，尾侧后脑GRP受体的可用性对于外周给药GRP-(18-27)减少大鼠的食物摄入量是必要的。
Bombesin (BN)-like peptides injected peripherally or centrally suppress food intake in rats. The relationship between the central and peripheral actions of BN is unknown. However, experimental evidence supports a critical role for the caudal hindbrain in mediating the feeding effects of BN. To investigate this relationship further, we examined the ability of fourth ventricular infusion of a specific gastrin-releasing peptide (GRP) antagonist; [D-F-5,Phe(6),D-Ala(11)]BN-(6-13)methyl ester (BN-ME), to block suppression of glucose intake (0.5 kcal/ml) produced by intraperitoneal administration of GRP-(18-27) in 5-h food-deprived male Sprague-Dawley rats (n = 10). We found that fourth ventricular administration of 10, 32, and 100 ng BN-ME blocked the suppression of glucose intake produced by peripherally administered 10 nmol/kg GRP-(18-27). The most effective dose of BN-ME (100 ng) blocked the ability of peripheral injection of GRP-(18-27) to inhibit glucose intake but had no effect on intake when given alone. These results demonstrate-that the availability of caudal hindbrain GRP receptors is necessary for peripherally administered GRP-(18-27) to reduce food intake in rats.