Background: Polysomnography (PSG) tests are very complicated and time consuming, despite their clinical benefits in the diagnosis of patients with obstructive sleep apnea hypopnea syndrome (OSAHS). A plasma marker would be desirable to select patients suspected of OSAHS for further PSG studies. We have recently reported that orexin-A concentrations in plasma collected immediately after waking early in the morning were significantly lower in patients with OSAHS than in controls. Objectives: We conducted the present study to assess the clinical usefulness of the measurement of orexin-A concentrations in plasma obtained in the daytime as a diagnostic predictor to screen patients with OSAHS. Methods: Blood samples were collected in the daytime from 19 male patients with suspected sleep-disordered breathing. Plasma orexin-A concentrations were measured by radioimmunoassay before performing PSG. Results: PSG was conducted in all 19 subjects. PSG showed that 14 subjects had OSAHS and 5 subjects did not. Plasma orexin-A concentrations were significantly lower in patients with OSAHS (4.9 ± 0.8 pmol/l, mean ± SE, n = 14) than in control subjects (12.3 ± 1.9 pmol/l, n = 5) (p = 0.0004). Conclusions: These findings suggest that the orexin-A concentration in plasma obtained even in the daytime may be a useful plasma marker for screening OSAHS.

1.
Campfield LA, Smith FJ: The pathogenesis of obesity. Baillières Best Pract Res Clin Endocrinol Metab 1999;13:13–30.
2.
Wilson BD, Bagnol D, Kaelin CB, Ollmann MM, Gantz I, Watson SJ, Barsh GS: Physiological and anatomical circuitry between Agouti-related protein and leptin signaling. Endocrinology 1999;140:2387–2397.
3.
Manzella D, Parillo M, Razzino T, Gnasso P, Buonanno S, Gargiulo A, Caputi M, Paolisso G: Soluble leptin receptor and insulin resistance as determinant of sleep apnea. Int J Obes Relat Metab Disord 2002;26:370–375.
4.
Chin K, Shimizu K, Nakamura T, Narai N, Masuzaki H, Ogawa Y, Mishima M, Nakamura T, Nakao K, Ohi M: Changes in intra-abdominal visceral fat and serum leptin levels in patients with obstructive sleep apnea syndrome following nasal continuous positive airway pressure therapy. Circulation 1999;100:706–712.
5.
Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richarson JA, Kozlowski GP, Wilson S, Arch JR, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M: Orexins and orexin receptors: A family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 1998;92:573–585.
6.
de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg EL, Gautvik VT, Bartlett FS 2nd, Frankel WN, van den Pol AN, Bloom FE, Gautvik KM, Sutcliffe JG: The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 1998 ; 95:322–327.
7.
Lubkin M, Stricker-Krongrad A: Independent feeding and metabolic actions of orexins in mice. Biochem Biophys Res Commun 1998;253:241–245.
8.
Ida T, Nakahara K, Katayama T, Murakami N, Nakazato M: Effect of lateral cerebroventricular injection of the appetite-stimulating neuropeptide, orexin and neuropeptide Y, on the various behavioral activities of rats. Brain Res 1999;821:526–529.
9.
Haynes AC, Jackson B, Overend P, Buckingham RE, Wilson S, Tadayyon M, Arch JR: Effects of single and chronic intracerebroventricular administration of the orexins on feeding in the rat. Peptides 1999;20:1099–1105.
10.
Sweet DC, Levine AS, Billington CJ, Kotz CM: Feeding response to central orexins. Brain Res 1999;821:535–538.
11.
Volkoff H, Bjorklund JM, Peter RE: Stimulation of feeding behavior and food consumption in the goldfish, Carassius auratus, by orexin-A and orexin-B. Brain Res 1999;846:204–209.
12.
Sakurai T: Orexins and orexin receptors: Implication in feeding behavior. Regul Pept 1999;85:25–30.
13.
Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X, Qiu X, de Jong PJ, Nishino S, Mignot E: The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 1999;98:365–376.
14.
Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, Richardson JA, Williams SC, Xiong Y, Kisanuki Y, Fitch TE, Nakazato M, Hammer RE, Saper CB, Yanagisawa M: Narcolepsy in orexin knockout mice: Molecular genetics of sleep regulation. Cell 1999;98:437–451.
15.
Hungs M, Mignot E: Hypocretin/orexin, sleep and narcolepsy. Bioessays 2001;23:397–408.
16.
Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E: Hypocretin (orexin) deficiency in human narcolepsy. Lancet 2000;355:39–40.
17.
Thannickal TC, Moore RY, Nienhuis R, Ramanathan L, Gulyani S, Aldrich M, Cornford M, Siegel JM: Reduced number of hypocretin neurons in human narcolepsy. Neuron 2000;27:469–474.
18.
Kirchgessner AL: Orexins in the brain-gut axis. Endocr Rev 2002;23:1–15.
19.
Kirchgessner AL, Liu M: Orexin synthesis and response in the gut. Neuron 1999;24:941–951.
20.
Nakabayashi M, Suzuki T, Takahashi K, Totsune K, Muramatsu Y, Kaneko C, Date F, Takeyama J, Darnel AD, Moriya T, Sasano H: Orexin-A expression in human peripheral tissues. Mol Cell Endocrinol 2003;205:43–50.
21.
Arihara Z, Takahashi K, Murakami O, Totsune K, Sone M, Satoh F, Ito S, Mouri T: Immunoreactive orexin-A in human plasma. Peptides 2001;22:139–142.
22.
Kastin AJ, Akerstrom V: Orexin A but not orexin B rapidly enters brain from blood by simple diffusion. J Pharmacol Exp Ther 1999;289:219–223.
23.
Nishijima T, Sakurai S, Arihara Z, Takahashi K: Plasma orexin-A-like immunoreactivity in patients with sleep apnea hypopnea syndrome. Peptides 2003;24:407–411.
24.
Igarashi N, Tatsumi K, Nakamura A, Sakao S, Takiguchi Y, Nishikawa T, Kuriyama T: Plasma orexin-A levels in obstructive sleep apnea-hypopnea syndrome. Chest 2003;124:1381–1385.
25.
Arihara Z, Takahashi K, Murakami O, et al: Orexin-A in the human brain and tumor tissues of ganglioneuroblastoma and neuroblastoma. Peptides 2000;21:565–570.
26.
Sleep-related breathing disorders in adults: Recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep. 1999;22:667–689.
27.
Johns MW: A new method for measuring daytime sleepiness: The Epworth sleepiness scale. Sleep 1991;14:540–545.
28.
Matsumura T, Nakayama M, Nomura A, Naito A, Kamahara K, Kadono K, Inoue M, Homma T, Sekizawa K: Age-related changes in plasma orexin-A concentrations. Exp Gerontol 2002;37:1127–1130.
29.
Sugimoto T, Nagake Y, Sugimoto S, Akagi S, Ichikawa H, Nakamura Y, Ogawa N, Makino H: Plasma orexin concentrations in patients on hemodialysis. Nephron 2002;90:379–383.
30.
Matsumura T, Nakayama M, Satoh H, Naito A, Kamahara K, Sekizawa K: Plasma orexin-A levels and body composition in COPD. Chest 2003;123:1060–1065.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.