![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 289, Issue 1, 219-223, April 1999
Veterans Affairs Medical Center and Tulane University School
of Medicine, New Orleans, Louisiana
We determined the ability of orexin A and orexin B, recently discovered
endogenous appetite enhancers, to cross the blood-brain barrier (BBB)
of mice. Multiple time-regression analysis showed that an i.v. bolus of
125I-orexin A rapidly entered the brain from the blood,
with an influx rate (Ki = 2.5 ± 0.3 × 10
4 ml/g·min) many times faster than that
of the 99mTc-albumin control. This relatively rapid rate of
entry was not reduced by administration of excess orexin A (or leptin)
or by fasting for 22 h, even when penetration into only the
hypothalamus was measured. Lack of saturability also was shown by
perfusion in blood-free buffer. HPLC revealed that most of the injected 125I-orexin A reached the brain as intact peptide.
Capillary depletion studies showed that the administered peptide did
not remain bound to the endothelial cells comprising the BBB but
reached the brain parenchyma. Efflux of 125I-orexin A from
the brain occurred at the same rate as 99mTc-albumin. The
octanol/buffer partition coefficient of 0.232 showed that orexin A was
highly lipophilic, whereas the value for orexin B was only 0.030. Orexin B, moreover, was rapidly degraded in blood, so no
125I-orexin B could be detected in intact form in brain
when injected peripherally. Thus, although orexin B is rapidly
metabolized in blood and has low lipophilicity, orexin A rapidly
crosses the BBB from blood to reach brain tissue by the process of
simple diffusion.
This article has been cited by other articles:
|
|
 |
|
  M. Hallschmid and J. Born Revealing the Potential of Intranasally Administered Orexin A (Hypocretin-1) Mol. Interv., June 1, 2008; 8(3): 133 - 137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Deadwyler, L. Porrino, J. M. Siegel, and R. E. Hampson Systemic and Nasal Delivery of Orexin-A (Hypocretin-1) Reduces the Effects of Sleep Deprivation on Cognitive Performance in Nonhuman Primates J. Neurosci., December 26, 2007; 27(52): 14239 - 14247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Silveyra, V. Lux-Lantos, and C. Libertun Both orexin receptors are expressed in rat ovaries and fluctuate with the estrous cycle: effects of orexin receptor antagonists on gonadotropins and ovulation Am J Physiol Endocrinol Metab, October 1, 2007; 293(4): E977 - E985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. W. Bengtsson, K. Makela, M. Sjoblom, S. Uotila, K. E. O. Akerman, K.-H. Herzig, and G. Flemstrom Food-induced expression of orexin receptors in rat duodenal mucosa regulates the bicarbonate secretory response to orexin-A Am J Physiol Gastrointest Liver Physiol, August 1, 2007; 293(2): G501 - G509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Tanida, A. Niijima, J. Shen, S. Yamada, H. Sawai, Y. Fukuda, and K. Nagai Dose-different effects of orexin-a on the renal sympathetic nerve and blood pressure in urethane-anesthetized rats. Experimental Biology and Medicine, November 1, 2006; 231(10): 1616 - 1625. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Kastin and W. Pan Intranasal Leptin: Blood-Brain Barrier Bypass (BBBB) for Obesity? Endocrinology, May 1, 2006; 147(5): 2086 - 2087. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Spinazzi, P. G. Andreis, G. P. Rossi, and G. G. Nussdorfer Orexins in the regulation of the hypothalamic-pituitary-adrenal axis. Pharmacol. Rev., March 1, 2006; 58(1): 46 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. R. Holland, S. Akerman, and P. J. Goadsby Orexin 1 Receptor Activation Attenuates Neurogenic Dural Vasodilation in an Animal Model of Trigeminovascular Nociception J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1380 - 1385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ehrstrom, T. Gustafsson, A. Finn, A. Kirchgessner, P. Gryback, H. Jacobsson, P. M. Hellstrom, and E. Naslund Inhibitory Effect of Exogenous Orexin A on Gastric Emptying, Plasma Leptin, and the Distribution of Orexin and Orexin Receptors in the Gut and Pancreas in Man J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2370 - 2377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. John, M.-F. Wu, N. T Maidment, H. A Lam, L. N Boehmer, M. Patton, and J. M Siegel Developmental changes in CSF hypocretin-1 (orexin-A) levels in normal and genetically narcoleptic Doberman pinschers J. Physiol., October 15, 2004; 560(2): 587 - 592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kiwaki, C. M. Kotz, C. Wang, L. Lanningham-Foster, and J. A. Levine Orexin A (hypocretin 1) injected into hypothalamic paraventricular nucleus and spontaneous physical activity in rats Am J Physiol Endocrinol Metab, April 1, 2004; 286(4): E551 - E559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Igarashi, K. Tatsumi, A. Nakamura, S. Sakao, Y. Takiguchi, T. Nishikawa, and T. Kuriyama Plasma Orexin-A Levels in Obstructive Sleep Apnea-Hypopnea Syndrome Chest, October 1, 2003; 124(4): 1381 - 1385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Nonaka, S. Shioda, M. L. Niehoff, and W. A. Banks Characterization of Blood-Brain Barrier Permeability to PYY3-36 in the Mouse J. Pharmacol. Exp. Ther., September 1, 2003; 306(3): 948 - 953. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ammoun, T. Holmqvist, R. Shariatmadari, H. B. Oonk, M. Detheux, M. Parmentier, K. E. O. Akerman, and J. P. Kukkonen Distinct Recognition of OX1 and OX2 Receptors by Orexin Peptides J. Pharmacol. Exp. Ther., May 1, 2003; 305(2): 507 - 514. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Shirasaka, M. Takasaki, and H. Kannan Cardiovascular effects of leptin and orexins Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2003; 284(3): R639 - R651. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ouedraogo, E. Naslund, and A. L. Kirchgessner Glucose Regulates the Release of Orexin-A From the Endocrine Pancreas Diabetes, January 1, 2003; 52(1): 111 - 117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Kukkonen, T. Holmqvist, S. Ammoun, and K. E. O. Akerman Functions of the orexinergic/hypocretinergic system Am J Physiol Cell Physiol, December 1, 2002; 283(6): C1567 - C1591. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-F. Wu, J. John, N. Maidment, H. A. Lam, and J. M. Siegel Hypocretin release in normal and narcoleptic dogs after food and sleep deprivation, eating, and movement Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2002; 283(5): R1079 - R1086. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-C. Xi, S. J. Fung, J. Yamuy, F. R. Morales, and M. H. Chase Induction of Active (REM) Sleep and Motor Inhibition by Hypocretin in the Nucleus Pontis Oralis of the Cat J Neurophysiol, June 1, 2002; 87(6): 2880 - 2888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Johren, S. J. Neidert, M. Kummer, A. Dendorfer, and P. Dominiak Prepro-Orexin and Orexin Receptor mRNAs Are Differentially Expressed in Peripheral Tissues of Male and Female Rats Endocrinology, August 1, 2001; 142(8): 3324 - 3331. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Dalal, A. Schuld, M. Haack, M. Uhr, P. Geisler, I. Eisensehr, S. Noachtar, and T. Pollmacher Normal plasma levels of orexin A (hypocretin-1) in narcoleptic patients Neurology, June 26, 2001; 56(12): 1749 - 1751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Kane, S. L. Parker, S. G. Matta, Y. Fu, B. M. Sharp, and M. D. Li Nicotine Up-Regulates Expression of Orexin and Its Receptors in Rat Brain Endocrinology, October 1, 2000; 141(10): 3623 - 3629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Kastin and V. Akerstrom Mahogany (1377-1428) Enters Brain by a Saturable Transport System J. Pharmacol. Exp. Ther., August 1, 2000; 294(2): 633 - 636. [Abstract] [Full Text]
|
|
|
|
|
|
A. J. Kastin and V. Akerstrom Entry of CART into brain is rapid but not inhibited by excess CART or leptin Am J Physiol Endocrinol Metab, November 1, 1999; 277(5): E901 - E904. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
