title: Calcium signals activated by ghrelin and D-Lys(3)-GHRP-6 ghrelin antagonist in developing dorsal root ganglion glial cells.
abstract: 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)-GHRP-6, indicate that DRG cells express GHSR-1a. In glial cells the response is characterized by a rapid transient rise in [Ca(2+)](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 Ca(2+) 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 Ca(2+) 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-Lys(3)-GHRP-6 ghrelin antagonist features ghrelin independent activities.
authors: Dipartimento di Scienze Chimiche Alimentari Farmaceutiche e Farmacologiche, Università del Piemonte Orientale A. Avogadro, Novara, Italy.
authors: Jessica
authors: J
authors: Erriquez
authors: Silvia
authors: S
authors: Bernascone
authors: Monica
authors: M
authors: Ciarletta
authors: Nicoletta
authors: N
authors: Filigheddu
authors: Andrea
authors: A
authors: Graziani
authors: Carla
authors: C
authors: Distasi
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D002642:Chick Embryo; D002645:Chickens; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D054439:Ghrelin / Q000494:pharmacology*; D009457:Neuroglia / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology*; D054440:Receptors, Ghrelin / Q000235:genetics / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; C520836:GHRP-6, Lys(3)-; D054439:Ghrelin; D009842:Oligopeptides; D054440:Receptors, Ghrelin; D019284:Thapsigargin; D002118:Calcium