Secretion of ghrelin from rat stomach ghrelin cells in response to local microinfusion of candidate messenger compounds:: A microdialysis study
Secretion of ghrelin from rat stomach ghrelin cells in response to local microinfusion of candidate messenger compounds:: A microdialysis study
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DOI：
10.1016/j.regpep.2007.05.001
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发表时间：
2007-10-04
影响因子：
--
通讯作者：
Hakanson, Rolf
中科院分区：
文献类型：
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作者：
de la Cour, Charlotta Domonville;Norlen, Per;Hakanson, Rolf
Ghrelin是由胃的产酸部分的粘膜中的类A细胞(Ghrelin细胞)产生的。Ghrelin的动员受到营养缺乏的刺激和营养丰富的抑制。为了确定可能有助于Ghrelin分泌的生理和营养相关调节的神经递质和调节肽，我们在原位用各种候选信使挑战Ghrelin细胞，包括已知的神经递质(例如乙酰胆碱、儿茶酚胺)、候选神经递质(例如神经肽)、局部组织激素(例如5-羟色胺、组胺、缓激肽、内皮素)、循环胃肠激素(例如胃泌素、CCK、GIP、神经紧张素、PYY、分泌素)和其他循环激素/调节多肽(例如降钙素、胰高血糖素、胰岛素、PTH)。将微透析探头放置在大鼠胃的产酸部的粘膜下层。3天后，通过微透析探针(反向微透析)给药，筛选剂量分别为0.1 mmol1(-1)的调节肽和0.1和1 mmol1(-1)的氨基酸。在实验过程中，老鼠是清醒的。微透析液中的Ghrelin浓度连续监测3小时(放射免疫法)，从而揭示Ghrelin分泌的刺激物或抑制物。对于在筛选剂量下显著影响Ghrelin动员的每个候选信使(p<；0.05)，构建了剂量-反应曲线。在筛选剂量下表现出影响Ghrelin释放的(不显著)趋势的多肽也在0.3或1 mmol1(-1)剂量下给药。肾上腺素、去甲肾上腺素、内皮素和促生长素促进Ghrelin的释放，而生长抑素和GRP抑制Ghrelin的释放。这些药物是否直接或间接作用于Ghrelin细胞仍有待调查。所有其他候选信使包括乙酰胆碱、5-羟色胺、组胺、GABA、天冬氨酸、谷氨酸、甘氨酸、VIP、PACAP、CGRP、P物质、NPY、PYY、PP、胃泌素、CCK、GIP、胰岛素、胰高血糖素、GLP和葡萄糖。(C)2007 Elsevier B.V.保留所有权利。
Ghrelin is produced by A-like cells (ghrelin cells) in the mucosa of the acid-producing part of the stomach. The mobilization of ghrelin is stimulated by nutritional deficiency and suppressed by nutritional abundance. In an attempt to identify neurotransmitters and regulatory peptides that may contribute to the physiological, nutrient-related regulation of ghrelin secretion, we challenged the ghrelin cells in situ with a wide variety of candidate messengers, including known neurotransmitters (e.g. acetylcholine, catecholamines), candidate neurotransmitters (e.g. neuropeptides), local tissue hormones (e.g. serotonin, histamine, bradykinin, endothelin), circulating gut hormones (e.g. gastrin, CCK, GIP, neurotensin, PYY, secretin) and other circulating hormones/regulatory peptides (e.g. calcitonin, glucagon, insulin, PTH). Microdialysis probes were placed in the submucosa of the acid-producing part of the rat stomach. Three days later, the putative messenger compounds were administered via the microdialysis probe (reverse microdialysis) at a screening dose of 0.1 mmol 1(-1) for regulatory peptides and 0.1 and 1 mmol 1(-1) for amines and amino acids. The rats were awake during the experiments. The resulting microdialysate ghrelin concentration was monitored continuously for 3 h (radioimmunoassay), thereby revealing stimulators or inhibitors of ghrelin secretion. Dose-response curves were constructed for each candidate messenger that significantly (p < 0.05) affected ghrelin mobilization at the screening dose. Peptides that showed a (non-significant) tendency to affect ghrelin release at the screening dose were also given at a dose of 0.3 or 1 mmol 1(-1). Adrenaline, noradrenaline, endothelin and secretin stimulated ghrelin release, while somatostatin and GRP inhibited. Whether these agents act directly or indirectly on the ghrelin cells remains to be investigated. All other candidate messengers were without measurable effects, including acetylcholine, serotonin, histamine, GABA, aspartic acid, glutamic acid, glycine, VIP, PACAP, CGRP, substance P, NPY, PYY, PP, gastrin, CCK, GIP, insulin, glucagon, GLP and glucose. (c) 2007 Elsevier B.V. All rights reserved.