title: 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.
authors.affiliation: Ghrelin Research Project, Translational Research Center, Kyoto University Hospital, Kyoto, Japan. hiwaku@kuhp.kyoto-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwakura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ariyasu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hosoda
authors.forename: Go
authors.initials: G
authors.lastname: Yamada
authors.forename: Kiminori
authors.initials: K
authors.lastname: Hosoda
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Akamizu
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004837:Epinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism; D019863:Gastrin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D054439:Ghrelin / Q000235:genetics / Q000378:metabolism*; D006727:Hormone Antagonists / Q000494:pharmacology; D051379:Mice; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism; D010121:Oxytocin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D054439:Ghrelin; D006727:Hormone Antagonists; D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D017447:Receptors, Dopamine D1; D018045:Receptors, Oxytocin; C098593:dopamine D1A receptor; D010121:Oxytocin; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine