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

Citation
D. Smart et al., The hypocretins are weak agonists at recombinant human orexin-1 and orexin-2 receptors, BR J PHARM, 129(7), 2000, pp. 1289-1291
Citations number
11
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BRITISH JOURNAL OF PHARMACOLOGY
ISSN journal
00071188 → ACNP
Volume
129
Issue
7
Year of publication
2000
Pages
1289 - 1291
Database
ISI
SICI code
0007-1188(200004)129:7<1289:THAWAA>2.0.ZU;2-6
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 (OX2) or orexin-2 (OX1) receptors by measuring intracellular calcium ([C a2+](i)) using Fluo-3AM. Orexin-A and orexin-B increased [Ca2+](i) in CHO-O X1 (pEC(50) = 7.99 +/- 0.05 and 7.00 +/- 0.10 respectively, n = 8) and CHO- OX2 (pEC(50) = 8.30 +/- 0.05 and 8.21 +/- 0.07 respectively, n = 5). Howeve r, hypocretin-1 and hypocretin-2 were markedly less potent, with pEC(50) va lues of 5.31 +/- 0.04 and 5.41 +/- 0.04 respectively in CHO-OX2 cells (n = 5). In CHO-OX1 cells 10 mu M, hypocretin-1 only elicited a 37.5 +/- 3.4% re sponse whilst 10 mu M hypocretin-2 elicited a 18.0 +/- 2.1% response (n = 8 ). Desensitisation of OX1 or OX2 with orexin-A (100 nM) abolished the respo nse to orexin-A (10 nM) and the hypocretins (10 mu M), but not to UTP (3 mu M). In conclusion, the hypocretins are only weak agonists at the orexin re ceptors.