title: Kisspeptin-10 elicits triphasic cytosolic calcium responses in immortalized GT1-7 GnRH neurones.
abstract: Kisspeptins, which are alternatively called as metastin since they were originally identified as products of metastasis suppressor gene KiSS-1, are the natural ligands for the G protein-coupled receptor 54 (GPR54). Kisspeptins are the most potent activators of hypothalamic-pituitary-gonadal (HPG) axis reported to date. The pulsatile pattern of GnRH release, which results in the intermittent release of gonadotropic hormones from the pituitary, has a critical importance for reproductive function but the factors responsible from this release pattern are not known. Therefore, the pattern of kisspeptin-induced intracellular signaling and the role of PKC in the intracellular signaling cascade were investigated by fluorescence calcium imaging using the immortalized GnRH-secreting GT1-7 hypothalamic neurons. Kisspeptin-10 caused a triphasic change characterized by an initial small increase followed by a significant decrease and increase in intracellular free calcium concentrations ([Ca(2+)](i)). The changes in [Ca(2+)](i) were significantly attenuated by pre-treatment with protein kinase C inhibitor. The compatibility of appeared mirrored-patterns of kisspeptin-10-induced changes in [Ca(2+)](i) concentrations in these neurons and GnRH secretion confirm the importance of intracellular calcium flux downstream from GPR54 through PKC signaling pathway.
authors.affiliation: Firat University, Medical School, Department of Biophysics, Elazig, Turkey.
authors.forename: Mete
authors.initials: M
authors.lastname: Ozcan
authors.forename: Ergul
authors.initials: E
authors.lastname: Alcin
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ayar
authors.forename: Bayram
authors.initials: B
authors.lastname: Yilmaz
authors.forename: Suleyman
authors.initials: S
authors.lastname: Sandal
authors.forename: Haluk
authors.initials: H
authors.lastname: Kelestimur
mesh_terms: D053119:Benzophenanthridines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002461:Cell Line, Transformed; D003600:Cytosol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D059648:Kisspeptins; D009474:Neurons / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*
chemical_list: D053119:Benzophenanthridines; C106628:KISS1 protein, human; D059648:Kisspeptins; D025521:Tumor Suppressor Proteins; D007987:Gonadotropin-Releasing Hormone; C016299:chelerythrine; D002118:Calcium