Uses
Spadin is an anti-depressant molecule that blocks TREK-1 potassium channels.
Biological Activity
spadin is a potent trek-1 channel inhibitor with ic50 of 71nm. it is a secreted peptide derived from the propeptide generated by the maturation of ntsr3/sortilin. [1]trek-1, aka kcnk2, is a two-pore domain ion channel that involved in the passive transmembrane k+ transport. it is related to the ischemia, anesthesia and electrogenesis in the neurons. it also plays an important role in the pathophysiological process of depression and in the response to antidepressant. [1]in trek-1 transfected cos-7 cells, 100nm of spadin inhibited 63% of the trek-1 current stimulated by arachidnice acid. spadin also blocked the trek-1 channels activity in ca3 hippocampal neurons on brain slices of wild-type mice. [1]in behavioral tests that predicting an antidepressant response, spadin-treated mice displayed a resistance to depression. mice treated with spadin for 4 days also exhibited a significant antidepressant effect as well as elevated hippocampal phosphorylation of creb protein and neurogenesis. [2]
References
1. borsotto m, veyssiere j, moha ou maati h et al. targeting two-pore domain k(+) channels trek-1 and task-3 for the treatment of depression: a new therapeutic concept. br j pharmacol. 2015 feb;172(3):771-84.2. mazella j, pétrault o, lucas g, et al. spadin, a sortilin-derived peptide, targeting rodent trek-1 channels: a new concept in the antidepressant drug design. plos biol. 2010 apr 13;8(4):e1000355.
