title: Lack of interaction between orexinergic and alpha2-adrenergic neuronal systems in rat cerebrocortical slices.
abstract: Orexinergic and norepinephrinergic alpha2-adrenoceptor expressing neurons contribute to the regulation of the sleep-wakefulness cycle. In the present study, we have examined a possible interaction between orexinergic and alpha2-adrenergic systems in orexin-A (100 nM)- and K+ (25 mM)-evoked norepinephrine release from slices of rat cerebrocortex. In this tissue norepinephrinergic neurons are predominantly innervated via the locus coeruleus. Clonidine concentration-dependently inhibited K+-evoked norepinephrine release with pIC50 (Imax) of 6.44+/-0.38 (48.8+/-6.9%). A selective orexin-1 receptor antagonist, SB-334867 was ineffective. SB-334867 concentration-dependently inhibited orexin A-evoked norepinephrine release with pIC50 (Imax) of 6.05+/-0.14 (86.4+/-5.4%); clonidine (alpha2-agonist) was ineffective. In contrast, yohimbine reversed the inhibitory effects of clonidine (1 microM) on K+-evoked norepinephrine release with pIC50 (Imax) of 6.50+/-0.34 (77.6+/-10.9%); orexin A was ineffective. The present data suggest a lack of interaction between orexinergic and alpha2-adrenergic neurons in rat cerebral cortex.
authors.affiliation: Department of Anesthesiology, University of Hirosaki School of Medicine, Hirosaki 036-8563, Japan. masuika@cc.hirosaki-u.ac.jp
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Hirota
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kudo
authors.forename: Ryuji
authors.initials: R
authors.lastname: Tose
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kudo
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kushikata
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects / Q000378:metabolism*; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009287:Naphthyridines; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D064446:Orexin Receptors; D000068797:Orexins; D009924:Organ Culture Techniques; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001583:Benzoxazoles; D047908:Intracellular Signaling Peptides and Proteins; D009287:Naphthyridines; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D018341:Receptors, Adrenergic, alpha-2; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D015016:Yohimbine; D014508:Urea; D003000:Clonidine; D011188:Potassium; D009638:Norepinephrine