The hypocretins are weak agonists at recombinant human orexin‐1 and orexin‐2 receptors
- 1 April 2000
- journal article
- Published by Wiley in British Journal of Pharmacology
- Vol. 129 (7), 1289-1291
- https://doi.org/10.1038/sj.bjp.0703257
Abstract
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 microM hypocretin-1 only elicited a 37.5+/-3.4% response whilst 10 microM 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 microM), but not to UTP (3 microM). In conclusion, the hypocretins are only weak agonists at the orexin receptors.Keywords
This publication has 11 references indexed in Scilit:
- Orexins: a new family of neuropeptidesBritish Journal of Anaesthesia, 1999
- Characterization of recombinant human orexin receptor pharmacology in a Chinese hamster ovary cell‐line using FLIPRBritish Journal of Pharmacology, 1999
- Cardiovascular regulatory actions of the hypocretins in brainBrain Research, 1999
- Hypothalamic Hypocretin (Orexin): Robust Innervation of the Spinal CordJournal of Neuroscience, 1999
- Measurement of [Ca2+] Using the Fluorometric Imaging Plate Reader (FLIPR)Published by Springer Nature ,1998
- Neurons Containing Hypocretin (Orexin) Project to Multiple Neuronal SystemsJournal of Neuroscience, 1998
- Obesity and the Hypothalamus: Novel Peptides for New PathwaysCell, 1998
- Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding BehaviorCell, 1998
- The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activityProceedings of the National Academy of Sciences, 1998
- Molecular mechanisms of membrane receptor desensitizationBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1993