The hypocretins are weak agonists at recombinant human orexin-1 and orexin-2 receptors.
Br J Pharmacol
; 129(7): 1289-91, 2000 Apr.
Article
in En
| MEDLINE
| ID: mdl-10742282
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, Neuropeptide
/
Neurotransmitter Agents
/
Intracellular Signaling Peptides and Proteins
Limits:
Animals
/
Humans
Language:
En
Journal:
Br J Pharmacol
Year:
2000
Document type:
Article
Affiliation country:
United kingdom