The Effect Of Orexin System On Brain Cells Of Different Species And Other Cell Lines

Introduction The orexin system is implicated in many physiological functions such as sleep wakefulness, feeding and appetite and neuroendocrine regulation. Disturbance of this system can lead to several pathological conditions for example, narcolepsy, cataplexy and obesity. This system is composed of two orexin peptides A and B that bind to two receptors; orexin receptor 1 (OX1R) and 2 (OX2R). As they belong to G protein-coupled receptors (GPCRs), they can share their signalling pathways. In the recent decade, in many GPCR evidence has accumulated for functional selectivity, the term that means different agonists (or antagonists) can induce different conformations at the same receptor and therefore can selectively activate different signalling pathway. Until now, no studies for differential selectivity of orexin A and B or other antagonists at orexin receptors have been reported. However, many studies have investigated the different signalling pathways of these receptors in brain cells of different species and other cell-lines. In order to investigate this functional selectivity at both orexin receptors, some time will be first taken in this review to discuss the structure, distribution of orexins and orexin receptors, the different signalling processes and some of orexin antagonists involved in this system. Orexin (hypocretin) peptides The two active peptides; orexin A and orexin B are structurally related to each other but have no sequence similarity to any other known