Kisspeptin-10

Kisspeptin-10 (KP-10, metastin 45-54) is a decapeptide, Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2 (C63H83N17O14, 1302.4 g/mol), corresponding to the C-terminal decapeptide amide of kisspeptin-54, the longest product of the KISS1 gene. The kisspeptins were isolated from placental tissue in 2001 as endogenous agonists of the previously orphan G protein-coupled receptor GPR54 (KISS1R), and the 54-, 14- and 13-residue forms share a common Arg-Phe-amide (RF-amide) C-terminus. KP-10 has been described as the biologically active C-terminal fragment, sharing the activities of the full-length peptide at GPR54.

Kisspeptin-10 in the research literature

In receptor-expressing CHO cells, kisspeptins bound GPR54 with low nanomolar affinity and stimulated PIP2 hydrolysis, Ca2+ mobilization, arachidonic acid release and ERK1/2 and p38 MAP kinase phosphorylation. Much of the subsequent research has concerned hypothalamic signaling. In immortalized GT1-7 GnRH-secreting hypothalamic neurons, KP-10 produced a triphasic change in intracellular calcium that was attenuated by protein kinase C inhibition, and in perifusion studies it increased GnRH peak amplitude and duration.

Identified hypothalamic GnRH neurons were found to express GnRH, kisspeptin and GPR54 transcripts, and whole-cell patch-clamp recordings showed initial depolarization followed by increased action potential firing in response to kisspeptin. In mice, KiSS-1 mRNA was mapped to the anteroventral periventricular, periventricular and arcuate nuclei of the hypothalamus.