Oxytocin and Dopamine Stimulate Ghrelin Secretion by the Ghrelin-Producing Cell Line, MGN3-1 in Vitro

Oxytocin and Dopamine Stimulate Ghrelin Secretion by the Ghrelin-Producing Cell Line, MGN3-1 in Vitro
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DOI:
10.1210/en.2010-1455
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发表时间:
2011-07-01
期刊:
影响因子:
4.8
通讯作者:
Akamizu, Takashi
Akamizu, Takashi
中科院分区:
医学2区
文献类型:
--
作者:
Iwakura, Hiroshi;Ariyasu, Hiroyuki;Akamizu, Takashi

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为了了解ghrelin的生理作用,研究ghrelin的作用和ghrelin分泌的调节是至关重要的。虽然生长素释放肽的作用已被广泛揭示,但生长素释放肽产生细胞(X/A样细胞)调节生长素释放肽分泌的直接因素尚未完全了解。在这项研究中,我们研究了肽类激素和神经递质对体外生长激素释放肽分泌的影响,最近开发的生长激素释放肽生产细胞系MGN 3 -1。催产素和加压素显著刺激MGN 3 -1细胞分泌ghrelin。由于MGN 3 -1细胞仅表达催产素受体mRNA,而不表达加压素受体mRNA,因此催产素可能是调节剂,加压素的作用由交叉反应介导。我们还发现多巴胺以与先前已知的生长素释放肽刺激剂肾上腺素和去甲肾上腺素类似的方式刺激来自MGN 3 -1细胞的生长素释放肽分泌。MGN 3 -1细胞表达编码多巴胺受体D1 a和D2的mRNA。多巴胺受体D1激动剂非诺多泮刺激胃饥饿素分泌,而D2,D3激动剂溴隐亭没有。此外,D1受体拮抗剂SKF 83566减弱多巴胺的刺激作用。这些结果表明,多巴胺对ghrelin分泌的刺激作用是由D1 a受体介导的。总之,我们确定了两个直接调节ghrelin,催产素和多巴胺。这些发现将为进一步研究ghrelin的分泌调节提供新的方向,从而进一步了解ghrelin的生理作用。(内分泌学152:2619-2625,2011)
To understand the physiological role of ghrelin, it is crucial to study both the actions of ghrelin and the regulation of ghrelin secretion. Although ghrelin actions have been extensively revealed, the direct factors regulating ghrelin secretion by ghrelin-producing cells (X/A-like cells), however, is not fully understood. In this study, we examined the effects of peptide hormones and neurotransmitters on in vitro ghrelin secretion by the recently developed ghrelin-producing cell line MGN3-1. Oxytocin and vasopressin significantly stimulated ghrelin secretion by MGN3-1 cells. Because MGN3-1 cells express only oxytocin receptor mRNA, not vasopressin receptor mRNA, oxytocin is the likely regulator, with the effect of vasopressin mediated by a cross-reaction. We also discovered that dopamine stimulates ghrelin secretion from MGN3-1 cells in a similar manner to the previously known ghrelin stimulators, epinephrine and norepinephrine. MGN3-1 cells expressed mRNA encoding dopamine receptors D1a and D2. The dopamine receptor D1 agonist fenoldopam stimulated ghrelin secretion, whereas the D2, D3 agonist bromocriptine did not. Furthermore, the D1 receptor antagonist SKF83566 attenuated the stimulatory effect of dopamine. These results indicate that the stimulatory effect of dopamine on ghrelin secretion is mediated by the D1a receptor. In conclusion, we identified two direct regulators of ghrelin, oxytocin and dopamine. These findings will provide new direction for further studies seeking to further understand the regulation of ghrelin secretion, which will in turn lead to greater understanding of the physiological role of ghrelin. (Endocrinology 152: 2619-2625, 2011)