Inhibitory effects of an orexin-2 receptor antagonist on orexin A- and stress-induced ACTH responses in conscious rats.
Orexins, recognized for their diverse functions in sleep/wakefulness/arousal and appetite regulation, may play provocative roles in stress response. Although the PVN of the hypothalamus expresses an abundance of orexin-2 receptor (OX-2R), the involvement of OX-2R in regulating ACTH response to stress remains unclear. To address this, we examined effects of a selective antagonist to OX-2R (N-{(1S)-1-[6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]carbonyl}-2,2-dimethylpropyl)-N-{4-pyridinylmethyl}amine upon plasma ACTH concentrations after administration of orexin A and swimming stress. Increases in ACTH levels with orexin A or swimming stress were attenuated with prior administration of an OX-2R antagonist. These results suggest that swimming stress facilitates ACTH release, at least in part via activation of OX-2R.
Chang
Hyukki
H
Laboratory of Exercise Biochemistry, University of Tsukuba, Graduate School of Comprehensive Human Sciences, 1-1-1 Tennôdai, Tsukuba 305-8574, Ibaraki, Japan.
Saito
Tsuyoshi
T
Ohiwa
Nao
N
Tateoka
Masaru
M
Deocaris
Custer C
CC
Fujikawa
Takahiko
T
Soya
Hideaki
H
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003243:Consciousness / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D009490:Neurosecretory Systems / Q000187:drug effects / Q000378:metabolism*; D064446:Orexin Receptors; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors
C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D000324:Adrenocorticotropic Hormone