Pharmacological and chemical properties of astressin, antisauvagine-30 and α-helCRF: significance for behavioral experiments
Corticotropin releasing factor (CRF) represents an early chemical signal in the stress response and modulates various brain functions through G protein-coupled receptors. Two CRF receptor subtypes, CRF 1 and CRF 2, have been identified. Since the physicochemical properties of CRF receptor antagonist...
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Published in | Neuropharmacology Vol. 41; no. 4; pp. 507 - 516 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Elsevier Ltd
01.09.2001
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | Corticotropin releasing factor (CRF) represents an early chemical signal in the stress response and modulates various brain functions through G protein-coupled receptors. Two CRF receptor subtypes, CRF
1 and CRF
2, have been identified. Since the physicochemical properties of CRF receptor antagonists might influence their biological potency, the peptidic antagonists astressin, α-helical CRF
9–41 (α-helCRF) and antisauvagine-30 (aSvg-30) have been analyzed.
The rank order of solubility of these compounds in artificial cerebrospinal fluid (aCSF, pH 7.4) was aSvg-30>α-helCRF>>astressin, whereas the rank order of relative lipophilicity as determined with RP–HPLC was α-helCRF>astressin>aSvg-30. The calculated isoelectric points were 4.1 (α-helCRF), 7.4 (astressin) and 10.0 (aSvg-30). According to Schild analysis of the CRF receptor-dependent cAMP production of transfected HEK cells, aSvg-30 exhibited a competitive antagonism and displayed a 340 fold selectivity for mCRF
2β receptor. For astressin, however, the pharmacodynamic profile could not be explained by a simple competitive mechanism as indicated by Schild slopes >1 for rCRF
1 or mCRF
2β receptor. Behavioral experiments demonstrated that after i.c.v. injection, α-helCRF reduced oCRF-induced anxiety-like behavior in the elevated plus-maze, whereas astressin, despite its higher in vitro potency, did not. These findings could be explained by different physicochemical properties of the antagonists employed. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0028-3908 1873-7064 |
DOI: | 10.1016/S0028-3908(01)00094-6 |