Calcium signals activated by ghrelin and D-LyS3-GHRP-6 ghrelin antagonist in developing dorsal root ganglion glial cells

被引:23
作者
Erriquez, Jessica [1 ]
Bernascone, Silvia [1 ]
Ciarletta, Monica [1 ]
Filigheddu, Nicoletta [2 ]
Graziani, Andrea [2 ]
Distasi, Carla [1 ,3 ]
机构
[1] Univ Piemonte Orientale, Dipartimento Sci Chim Alimentari Farmaceut & Farm, I-28100 Novara, Italy
[2] Univ Piemonte Orientale, Dipartimento Med Clin & Sperimentale, I-28100 Novara, Italy
[3] Univ Turin, Ctr Interdipartimentale Studi Avanzati Neurosci, Turin, Italy
关键词
Dorsal root ganglion; Glial cells; Chick embryo; Ghrelin; D-LyS(3)-GHRP-6; GHSR-1a; Calcium signalling; SOCE; RACE; Apoptosis; RECIPROCAL REGULATION; ENTRY PATHWAYS; NEURAL CREST; NUCLEUS; CHICKEN; DIFFERENTIATION; NEUROGENESIS; INHIBITION; MECHANISMS; SECRETION;
D O I
10.1016/j.ceca.2009.07.003
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Ghrelin is a hormone regulating energy homeostasis via interaction with its receptor, GHSR-1a. Ghrelin activities in dorsal root ganglia (DRG) cells are unknown. Herein we show that ghrelin induces a change of cytosolic calcium concentration in both glia and neurons of embryonic chick DRG. Both RT-PCR and binding studies performed with fluorescent ghrelin in the presence of either unlabeled ghrelin or GHSR-1a antagonist D-Lys(3)-CHRP-6, indicate that DRG cells express GHSR-1a. In glial cells the response is characterized by a rapid transient rise in [Ca2+](i) followed by a long lasting rise. The calcium elevation is dependent on calcium release from thapsigargin-sensitive intracellular stores and on activation of two distinct Ca2+ entry pathways, a receptor activated calcium entry and a store operated calcium entry. Surprisingly, D-LyS(3)-GHRP-6 exerts several activities in the absence of exogenous ghrelin: (i) it activates calcium release from thapsigargin-sensitive intracellular stores and calcium entry via voltage-operated channels in non-neuronal cells; (ii) it inhibits calcium oscillations in non-neuronal cells exhibiting spontaneous Ca2+ activity and iii) it promotes apoptosis of DRG cells, both neurons and glia. In summary, we provide the first evidence for ghrelin activity in DRG, and we also demonstrate that the widely used D-LyS3-GHRP-6 ghrelin antagonist features ghrelin independent activities. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:197 / 208
页数:12
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