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

Abstract

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) G hrelin is a stomach-derived 28-amino acid peptide hormone with a unique modification of acylation, first described by Kojima et al. in 1999 (1). To understand better the physiological function of ghrelin, it is crucial to study both ghrelin action and the regulation of ghrelin secretion. The actions of ghrelin have been vigorously investigated by multiple groups, revealing a wide variety of activities, including GH-stimulating (2), orexigenic (3), fat-storing (4), cardiovascular (5), gastroprokinetic (6), and insulin-suppressing (7) activities. In contrast, the regulation of ghrelin secretion from ghrelin-producing cells (X/A-like cells) is not fully understood. Although the results of in vivo studies suggest that plasma ghrelin levels are regulated by acute and chronic energy status (8 -10), the individual factors regulating ghrelin secretion by ghrelin-producing cells (X/A-like cells) remains unclear due to the lack of an appropriate in vitro assay system.Recently we established a ghrelin-producing cell line, MGN (mouse ghrelinoma) 3-1 cells from a gastric ghrelinoma isolated from ghrelin promoter SV40-T antigen transgenic mice (11, 12). The MGN3-1 cell is the first cell line derived from a gastric ghrelin-producing cell that preserves the ability to secrete of substantial amounts of ghrelin under physiological regulation, making this line one of Abbre...

Surviving Starvation: Essential Role of the Ghrelin-Growth Hormone Axis

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β1-Adrenergic receptor deficiency in ghrelin-expressing cells causes hypoglycemia in susceptible individuals

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Distribution of ghrelin-positive mast cells in rat stomach

“…These results are supported by high levels of b1-adrenergic receptor expression in ghrelin cells of the stomach. Thus, sympathetic nerves stimulate directly ghrelin secretion [69][70][71][72]. According to Yang et al [73], ghrelin may regulate gastric smooth muscle contraction induced by cholinergic neurotransmitters using GHS-R1s, which are expressed on myenteric nerve cells, interstitial cells of Cajal and smooth muscle cells.…”