Orexins A and B are a pair of neuropeptides that act on two G protein-coupled receptors, orexin receptor-1 (OX1R) and -2 (OX2R), to regulate sleep and wakefulness. Orexin 2 receptor agonist potently activates OX2R with an EC50 value of 23 nM compared to OX1R (EC50 of 1.616 μM). The Emax of orexin 2 receptor agonist against OX2R was 98%. In CHO cells overexpressing hOX1R and HEK-293 cells overexpressing hOX2R, orexin 2 receptor agonist bound to hOX2R and hOX1R with Ki values of 0.14 μM and 0.77 μM, respectively[2]. In orexin receptor-expressing CHO cells, treatment of orexin 2 receptor agonist led to a robust Ca2+ response with 17.6-fold higher potency for OX2R than for OX1R. The response to orexin 2 receptor agonist was fully inhibited by 1 μM of Gq/11 inhibitor UBO-QIC. Orexin 2 receptor agonist also stimulated adenylyl cyclase activity in CHO cells treated with pertussis toxin and GF1092203X[3].
作用机制
The binding of orexin 2 receptor agonist to OX2R induces the inward movements of transmembrane helix 5 and 6, allowing the activity of orexin 2 receptor agonist against OX2R[2].
搜索
