title: Hypocretin-1 potentiates NMDA receptor-mediated somatodendritic secretion from locus ceruleus neurons.
abstract: Our previous observations showed that several stimuli, including high-K(+) solution, glutamate, and voltage pulses, induce somatic noradrenaline (NA) secretion from locus ceruleus (LC) neurons. Hypocretin (orexin), a hypothalamic peptide critical for normal wakefulness, has been shown to evoke NA release from the axon terminals of LC neurons. Here, we used amperometry to test the effect of hypocretin-1 (HCRT) on NMDA receptor-mediated somatodendritic release in LC neurons. Either HCRT or NMDA applied alone dose-dependently induced somatodendritic secretion. Bath application of HCRT notably potentiated NMDA receptor-mediated somatodendritic NA release. This potentiation was blocked by SB 334867, a selective HCRT receptor (Hcrtr 1) antagonist, or bisindolylmaleimide, a specific protein kinase C (PKC) inhibitor, indicating the involvement of Hcrtr 1 and PKC. Consistent with this, phorbol 12-myristate 13-acetate, a PKC activator, mimicked the HCRT-induced potentiation. Furthermore, HCRT enhanced NMDA-induced intracellular Ca(2+) elevation via activation of Hcrtr 1 and PKC, which may contribute to HCRT-potentiated somatodendritic secretion. These results suggest that HCRT modulates LC activity not only by regulating noradrenergic input to its targets, but also by affecting noradrenergic communication in the soma and dendrites.
authors: Department of Physiology, Third Military Medical University, Chongqing 400038, China.
authors: Xiao-Wei
authors: XW
authors: Chen
authors: Yu
authors: Y
authors: Mu
authors: Hong-Ping
authors: HP
authors: Huang
authors: Ning
authors: N
authors: Guo
authors: Bo
authors: B
authors: Zhang
authors: Shuang-Yi
authors: SY
authors: Fan
authors: Jia-Xiang
authors: JX
authors: Xiong
authors: Shi-Rong
authors: SR
authors: Wang
authors: Wei
authors: W
authors: Xiong
authors: Wei
authors: W
authors: Huang
authors: Tao
authors: T
authors: Liu
authors: Liang-Hong
authors: LH
authors: Zheng
authors: Claire Xi
authors: CX
authors: Zhang
authors: Li-Huan
authors: LH
authors: Li
authors: Zheng-Ping
authors: ZP
authors: Yu
authors: Zhi-An
authors: ZA
authors: Hu
authors: Zhuan
authors: Z
authors: Zhou
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008125:Locus Coeruleus / Q000166:cytology*; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology*; D009479:Neuropeptides / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D000068797:Orexins; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D000068797:Orexins; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D002118:Calcium