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Corticotropin and Adrenal Steroids

Unidirectional Specific and Modulated Brain to Blood Transport of Corticotropin-Releasing Hormone

Martins J.M. · Kastin A.J. · Banks W.A.

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Veterans Affairs Medical Center and Tulane University School of Medicine, New Orleans, La., USA

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Neuroendocrinology 1996;63:338–348

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Article / Publication Details

First-Page Preview
Abstract of Corticotropin and Adrenal Steroids

Received: August 25, 1995
Accepted: December 11, 1995
Published online: April 09, 2008
Issue release date: 1996

Number of Print Pages: 11
Number of Figures: 0
Number of Tables: 0

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: https://www.karger.com/NEN

Abstract

Corticotropin-releasing hormone (CRH) is produced and acts both within the central nervous system and at several peripheral sites. However, it is not known whether CRH is able to cross the blood-brain barrier (BBB) in either direction, or whether the central and peripheral compartments are independent. We studied the transport across the BBB of both human/rat CRH (hCRH) and ovine CRH (oCRH) using the native peptides labeled with 125I at the histidine residue, thereby avoiding the use of other synthetic modifications. No apparent transport of either hCRH or oCRH into the brain from blood was found, as measured by multiple-time regression analysis after intravenous injection of the labeled peptides. There were no significant differences between the two forms of the CRH peptide. However, both hCRH and oCRH were rapidly transported out of the brain after intracerebroventricular injection, with half-time (t½) disappearances of 11.1 (hCRH) and 15.1 min (oCRH); the transport rate was significantly different for the human and ovine forms. The transport of hCRH could be specifically inhibited by 5 nmol of unlabeled hCRH (t½ = 17.7 min) but not by the same dose of the synthetic analog αCRH12–41. The process could also be inhibited by pretreatment with aluminum chloride (t½ = 18.8 min). An indirect influence of the endogenous opiate modulating peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2 5 nmol) was apparent by a change in the initial distribution within the brain. In conclusion, there is a specific unidirectional brain to blood transport system for CRH. This transport system in the mouse has a greater affinity for the human/rat than for the ovine form of the peptide, is inhibited by hCRH itself, and can be disrupted by pretreatment with aluminum. By facilitating the rapid clearance of central CRH, this transport system could be involved in the regulation of central CRH levels and could allow central CRH to reach the general circulation and act at peripheral sites.

© 1996 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Corticotropin and Adrenal Steroids

Received: August 25, 1995
Accepted: December 11, 1995
Published online: April 09, 2008
Issue release date: 1996

Number of Print Pages: 11
Number of Figures: 0
Number of Tables: 0

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: https://www.karger.com/NEN


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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.
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