Ghrelin Is an Essential Factor for Motilin-Induced Gastric Contraction in Suncus murinus.
Ghrelin Is an Essential Factor for Motilin-Induced Gastric Contraction in Suncus murinus.
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DOI：
10.1210/en.2015-1561
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发表时间：
2015-10
期刊：
影响因子：
4.8
通讯作者：
K. Kuroda;Huang Hequing;A. Mondal;Makoto Yoshimura;Kazuma Ito;Takashi Mikami;Shota Takemi;T. Jogahara;I. Sakata;T. Sakai
中科院分区：
文献类型：
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作者：
K. Kuroda;Huang Hequing;A. Mondal;Makoto Yoshimura;Kazuma Ito;Takashi Mikami;Shota Takemi;T. Jogahara;I. Sakata;T. Sakai
胃动素在20世纪70年代被发现是刺激胃强烈收缩的最重要的激素;然而，胃动素引起胃收缩的机制尚不清楚。在这里，我们确定了胃动素和ghrelin的协调行动，在空腹和餐后收缩的胃运动，使用家麝鼩（臭鼩目：食虫目，臭鼩命名为实验室菌株）。胃饥饿素受体拮抗剂（D-Lys（3））-GHRP-6（6 mg/kg/h）预处理可抑制胃动素诱导的移行性复合运动I和II相胃收缩。胃动素受体拮抗剂MA-2029（0.1 mg/kg）和（D-Lys（3））-GHRP-6（0.6 mg/kg）在III相峰时给药可消除体内自发性胃III相收缩。胃动素在餐后状态下不刺激胃收缩。然而，在低剂量的ghrelin的存在下，胃动素诱发III相样胃收缩，即使在餐后状态，和餐后胃排空加速。此外，（D-Lys（3））-GHRP-6预处理可阻断胃动素诱导的离体和在体胃收缩，γ-氨基丁酸（GABA）拮抗剂可逆转这种阻断作用。这些结果表明，阻断GABA能途径的胃饥饿素是必不可少的胃动素诱导的胃收缩。
Motilin was discovered in the 1970s as the most important hormone for stimulating strong gastric contractions; however, the mechanisms by which motilin causes gastric contraction are not clearly understood. Here, we determined the coordinated action of motilin and ghrelin on gastric motility during fasted and postprandial contractions by using house musk shrew (Suncus murinus; order: Insectivora, suncus named as the laboratory strain). Motilin-induced gastric contractions at phases I and II of the migrating motor complex were inhibited by pretreatment with (D-Lys(3))-GHRP-6 (6 mg/kg/h), a ghrelin receptor antagonist. Administration of the motilin receptor antagonist MA-2029 (0.1 mg/kg) and/or (D-Lys(3))-GHRP-6 (0.6 mg/kg) at the peak of phase III abolished the spontaneous gastric phase III contractions in vivo. Motilin did not stimulate gastric contractions in the postprandial state. However, in the presence of a low dose of ghrelin, motilin evoked phase III-like gastric contractions even in the postprandial state, and postprandial gastric emptying was accelerated. In addition, pretreatment with (D-Lys(3))-GHRP-6 blocked the motilin-induced gastric contraction in vitro and in vivo, and a γ-aminobutyric acid (GABA) antagonist reversed this block in gastric contraction. These results indicate that blockade of the GABAergic pathway by ghrelin is essential for motilin-induced gastric contraction.