Immune Modulation Research
Research Only
PE 22-28
Also known as: PE 22-28, spadin analogue, TREK-1 blocker
Peptide inhibitor of the TREK-1 potassium channel. Studied in ion-channel and neuronal-signalling research.
Research overview
PE 22-28 is a synthetic seven-amino-acid peptide. It is a shortened version of spadin, a 17-amino-acid peptide that comes from the propeptide released when the protein sortilin (also called NTSR3) matures. Spadin was described, and PE 22-28 designed, by the Mazella, Borsotto and Heurteaux group at the CNRS in Valbonne, France, as blockers of TREK-1, a potassium channel. In cells carrying the human TREK-1 channel, PE 22-28 blocked it at much lower concentrations than spadin (Djillani et al., Front Pharmacol 2017). In the same study, treated mice spent less time immobile in the forced swim test and started eating sooner in the novelty-suppressed feeding test, two mouse tests used to model depression, and had more new nerve cells in the hippocampus.
All published work on PE 22-28 comes from this one research group and is in cells and mice. There are no published human studies, and its human pharmacokinetics and safety are unknown. Whether results in mouse behavioural tests apply to people is not known. Supplied for laboratory research use only.
Mechanism of action
PE 22-28 blocks TREK-1, a two-pore-domain potassium channel found on nerve cells and in other tissues. Its parent peptide spadin binds TREK-1 directly and, in mice, raised the firing rate of serotonin nerve cells in the dorsal raphe, a brainstem region (Mazella et al., PLoS Biol 2010). For PE 22-28 itself, the evidence comes from electrical recordings in cells carrying human TREK-1 and from mouse studies by the same group.