Kisspeptin-10 elicits triphasic cytosolic calcium responses in immortalized GT1-7 GnRH neurones

Neurosci Lett. 2011 Mar 29;492(1):55-8. doi: 10.1016/j.neulet.2011.01.054. Epub 2011 Jan 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzophenanthridines / pharmacology
  • Calcium / metabolism*
  • Cell Line, Transformed
  • Cytosol / metabolism*
  • Dose-Response Relationship, Drug
  • Gonadotropin-Releasing Hormone / metabolism*
  • Hypothalamus / metabolism
  • Kisspeptins
  • Neurons / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Tumor Suppressor Proteins / antagonists & inhibitors
  • Tumor Suppressor Proteins / pharmacology
  • Tumor Suppressor Proteins / physiology*


  • Benzophenanthridines
  • KISS1 protein, human
  • Kisspeptins
  • Tumor Suppressor Proteins
  • Gonadotropin-Releasing Hormone
  • chelerythrine
  • Calcium