PE 22-28 is a peptide inhibitor of the two-pore domain potassium channel K2P2.1/TREK1 (IC50 = 0.1 nM in HEK293 cells expressing the human channel) and a fragment of spadin .[1] It is selective for K2P2.1/TREK1 over K2P10.1 /TREK2, K2P13.1/TRAAK, K2P18.1/TRESK, and K2P3.1/TASK1 in HEK293 cells expressing the human channels at 100 nM. PE 22-28 (4 µg/kg for four days) increases neurogenesis and the levels of postsynaptic density protein 95 (Psd-95), a measure of increased synaptogenesis, in isolated mouse hippocampi. It decreases immobility in the forced swim test, latency to feed in the novelty-suppressed feeding test, and the time to escape in the Porsolt learned helplessness test in mice when administered at a dose of 0.3 µg/kg for four days.
References:
[1].Djillani, A., Pietri, M., Moreno, S., et al.Shortened spadin analogs display better TREK-1 inhibition, in vivo stability and antidepressant activityFront. Pharmacol.8:643(2017).