Orexin A and B evoke noradrenaline release from rat cerebrocortical slices

Orexin A and B, recently identified in the rat hypothalamus are endogenous neuropeptide agonists for the G‐protein coupled orexin‐1 (OX1) and orexin‐2 (OX2) receptors. In the present study, we have examined the effects of orexin A, B and raised extracellular K+ on noradrenaline release from the rat cerebrocortical slice. We have compared this with other sleep – wake‐related (excitatory) neurotransmitters; dopamine, glutamate, serotonin and histamine. Neurotransmitter release studies were performed in rat cerebrocortical slices incubated in modified Krebs buffer (with and without Ca2++EGTA 1 mM) with various concentrations of orexin A, B and K+ for various times. Orexin A and B‐evoked (10−7 M) noradrenaline release was time‐dependent reaching a maximum some 10 min after stimulation. K+ (40 mM) evoked release was also time dependent but reached a maximum after 6 min. Orexin A, B and K+ stimulation of release was concentration dependent with pEC50 and Emax (% of basal) values of 8.74±0.32 (1.8 nM) and 263±14% and 8.61±0.38 (2.4 nM) and 173±7% and 1.43±0.02 (37 mM) and 1430±70%, respectively. Orexin‐evoked release was partially extracellular Ca2+ dependent. Of the other transmitters studied there was a weak orexin A and B stimulation of glutamate release. In contrast K+ evoked dopamine, glutamate, histamine and serotonin release with pEC50 and Emax (% of basal) values of 1.47±0.05 (34 mM) and 3430±410%, 1.38±0.04 (42 mM) and 1240±50%, 1.47±0.02 (34 mM) and 480±10% and 1.40±0.05 (40 mM) and 560±60% respectively. We conclude that the neuropeptides orexin A and B evoke noradrenaline release from rat cerebrocortical slices. British Journal of Pharmacology (2001) 134, 1461–1466; doi:10.1038/sj.bjp.0704409