Planning sleep-related animal and translational research

With the aim of improving human health, scientists have been using an approach referred to as translational research, in which they aim to convey their laboratory discoveries into clinical applications to help prevent and cure disease. Such discoveries often arise from cellular, molecular, and physiological studies that progress to the clinical level. Most of the translational work is done using animal models that share common genes, molecular pathways, or phenotypes with humans. In this article, we discuss how translational work is carried out in various animal models and illustrate its relevance for human sleep research and sleep-related disorders

The hypocretins are weak agonists at recombinant human orexin-1 and orexin-2 receptors

The pharmacology of the orexin-like peptides, hypocretin-1 and hypocretin-2, was studied in Chinese hamster ovary (CHO) cells stably expressing orexin-1 (OX(1)) or orexin-2 (OX(2)) receptors by measuring intracellular calcium ([Ca(2+)](i)) using Fluo-3AM. Orexin-A and orexin-B increased [Ca(2+)](i) in CHO-OX(1) (pEC(50)=7.99±0.05 and 7.00±0.10 respectively, n=8) and CHO-OX(2) (pEC(50)=8.30±0.05 and 8.21±0.07 respectively, n=5). However, hypocretin-1 and hypocretin-2 were markedly less potent, with pEC(50) values of 5.31±0.04 and 5.41±0.04 respectively in CHO-OX(2) cells (n=5). In CHO-OX(1) cells 10 μM hypocretin-1 only elicited a 37.5±3.4% response whilst 10 μM hypocretin-2 elicited a 18.0±2.1% response (n=8). Desensitisation of OX(1) or OX(2) with orexin-A (100 nM) abolished the response to orexin-A (10 nM) and the hypocretins (10 μM), but not to UTP (3 μM). In conclusion, the hypocretins are only weak agonists at the orexin receptors