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The hypocretins are weak agonists at recombinant human orexin‐1 and orexin‐2 receptors
Author(s) -
Smart D,
Jerman J C,
Brough S J,
Neville W A,
Jewitt F,
Porter R A
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703257
Subject(s) - orexin , orexin receptor , chinese hamster ovary cell , orexin a , receptor , endocrinology , medicine , chemistry , neuropeptide , biology
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 μ M hypocretin‐1 only elicited a 37.5±3.4% response whilst 10 μ M hypocretin‐2 elicited a 18.0±2.1% response ( n =8). Desensitisation of OX 1 or OX 2 with orexin‐A (100 n M ) abolished the response to orexin‐A (10 n M ) and the hypocretins (10 μ M ), but not to UTP (3 μ M ). In conclusion, the hypocretins are only weak agonists at the orexin receptors. British Journal of Pharmacology (2000) 129 , 1289–1291; doi: 10.1038/sj.bjp.0703257