C6, a synthetic kisspeptin analog, produced longer-lasting calcium signaling but stronger tachyphylaxis than kisspeptin-10 or kisspeptin-54 in cells expressing the human kisspeptin receptor. It also drove the largest and most sustained changes in gene expression, including inflammatory genes, followed by hKp54 and then hKp10. The three agonists therefore have distinct in vitro pharmacological profiles.
Journal article — in vitro comparative pharmacology study. Population: HEK293 cells stably expressing the human Kp receptor. Interventions: C6.
C6 produced the most sustained Ca2+ mobilization and the most pronounced tachyphylaxis, which the authors propose stems from greater depletion of intracellular Ca2+ stores. A second low-concentration hKp54 challenge produced an increased response, whereas hKp10 did not. C6 also produced the strongest and most sustained transcriptional response, followed by hKp54 and hKp10, with marked upregulation of immediate-early genes, transcription factors, and inflammatory mediators.
This paper gives researchers working on Kisspeptin a direct head-to-head in vitro comparison of endogenous hKp10/hKp54 and synthetic C6, showing that they differ in calcium signaling, tachyphylaxis, and transcriptional outcomes. It highlights C6's stronger and more sustained activation but also its greater tachyphylaxis and inflammatory gene induction. It does not establish whether C6 is superior or safer in vivo, nor does it provide doses or clinical recommendations.
Peptide profiles: Kisspeptin.
All indexed evidence: Kisspeptin trials & papers.
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