Signaling pathways of hypocretin-1 actions on pyramidal neurons in the rat prefrontal cortex.
We have investigated the direct excitatory effects of hypocretin-1 on acutely isolated prefrontal cortical pyramidal neurons and explored the signaling mechanisms of these actions. Puff application of hypocretin-1 caused an excitation in the recorded neurons. These effects of hypocretin-1 were abolished by a phospholipase C inhibitor D609, demonstrating that phospholipase C mediates the actions of hypocretin-1. A specific protein kinase C inhibitor, bisindolylmaleimide II, blocked the excitatory actions of hypocretin-1, suggesting that protein kinase C plays a key role. Finally, protein kinase A inhibitor applied intracellularly did not affect the responses. These results indicate that hypocretin-1 excites prefrontal neurons by activation of phospholipase C and protein kinase C pathways, but not protein kinase A.
Song
Cheng-Hui
CH
Department of Neurobiology, Xinqiao Hospital, Chongqing, China.
Xia
Jian-Xia
JX
Ye
Jian-Ning
JN
Chen
Xiao-Wei
XW
Zhang
Chun-Qing
CQ
Zhang
Qing-Chun
QC
Gao
En-Quan
EQ
Hu
Zhi-An
ZA
D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D009479:Neuropeptides / Q000494:pharmacology*; D000068797:Orexins; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000166:cytology*; D011493:Protein Kinase C / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases