Fig. 2. Schematic diagram showing possible signaling pathways for kisspeptin in the central nervous system (CNS). The distinction is made between signaling through kisspeptin receptor (KISS1R), neuropeptide FF receptor (NPFFR) and possibly even other RFamide receptors. Signaling through KISS1R may be either an essential synaptic driver (gonadotropin-releasing hormone [GnRH] neurons) or neuromodulatory (proposed for other CNS neurons), whereas signaling through NPFFRs is suggested to be neuromodulatory throughout the CNS. The primary ion channels modulated by kisspeptin are noted for each mode of signaling. NSCC, non-selective cation ion channels; POMC, pro-opiomelanocortin; NCX, sodium-calcium exchanger; AMPA, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid.