Pharmacological and chemical properties of astressin, antisauvagine-30 and α-helCRF: significance for behavioral experiments

Brauns, Olaf; Liepold, Thomas; Radulovic, Jelena; Spiess, Joachim

doi:10.1016/s0028-3908(01)00094-6

Cited by 32 publications

(38 citation statements)

References 39 publications

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“…Thus, CRA1000 and CP-154,526 counteracted the adaptive changes in some system impacted by CRF during the repeated withdrawals from ethanol. A number of earlier reports implicated CRF 1 receptors in the anxiogenic effects of CRF or stress (e.g., Heinrichs et al, 1997;Landgraf, 2001) and in the anxiolytic effects of CRF receptor antagonists (Brauns et al, 2001;Radulovic et al, 1999;Seymour et al, 2003). The present results are consistent with these reports but add a new dimension.…”

Section: Discussionsupporting

confidence: 92%

“…Rats received intraventricular injections of antisauvagine-30 (20 μg) or artificial cerebrospinal fluid (5 μl) 4 h into the first and second withdrawals. The dose of antisauvagine-30 was selected on the basis of published reports (Brauns et al, 2001;Radulovic et al, 1999). The rat pairs were placed in the social interaction arena 5 h after the removal of ethanol.…”

Section: Intraventricular Administration Of Antisauvagine-30mentioning

confidence: 99%

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Modulation of multiple ethanol withdrawal-induced anxiety-like behavior by CRF and CRF1 receptors

Overstreet

Knapp

Breese

2004

Pharmacology Biochemistry and Behavior

159

153

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Previous work demonstrated that rats subjected to multiple withdrawals from chronic ethanol exhibit a sensitization of anxiety-like behavior compared to animals withdrawn from treatment with an equal but continuous amount of ethanol. This study sought to examine whether corticotropin-releasing factor (CRF) could modulate this ethanol-withdrawal-induced anxiety-like behavior. Initially, rats were administered with CRF (1 μg) or vehicle intraventricularly on two occasions 5 days apart while on control diet (CD) followed by exposure to 7% ethanol diet (ED) for 5 days, with social interaction assessed 5 h into withdrawal. Social interaction was significantly reduced in the CRF-treated animals compared to vehicle-treated rats and vehicle-and CRF-treated rats maintained on CD, indicative that CRF given before ethanol exposure was capable of inducing an adaptive change that sensitized withdrawal-induced anxiety-like behavior. Next, the CRF 1 receptor antagonist CRA1000 (3 mg/kg, systemically), the CRF 2 receptor antagonist antisauvagine-30 (20 μg intraventricularly), or vehicle was injected 4 h after the ethanol was removed following the first and second cycles of chronic ethanol exposure and the effect on the multiple-withdrawal-induced anxiety-like behavior determined after the third withdrawal cycle. The CRF 1 receptor antagonist blocked the reduced social interaction behavior, whereas the CRF 2 receptor antagonist was without effect. Similar pretreatment with another CRF 1 receptor antagonist CP-154,526 (10 mg/kg systemically) during the first and second withdrawals also counteracted anxiety-like behavior. These findings indicate that the CRF system and CRF 1 receptors play key roles in the adaptive change responsible for the anxiety-like behavior induced by repeated withdrawals from chronic ethanol.

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Section: Discussionsupporting

confidence: 92%

Section: Intraventricular Administration Of Antisauvagine-30mentioning

confidence: 99%

Modulation of multiple ethanol withdrawal-induced anxiety-like behavior by CRF and CRF1 receptors

Overstreet

Knapp

Breese

2004

Pharmacology Biochemistry and Behavior

159

153

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“…One application was the modification of the CRF antagonist astressin (Ast), whose employment in animal experiments is limited by its low solubility in cerebrospinal fluid. Introduction of Glu residues into Ast generated with [Glu 11,16 ]Ast an acidic astressin, which efficiently antagonized in vivo the CRFR1-dependent reduction of locomotion induced by ovine CRF without detectable binding to CRFBP. …”

mentioning

confidence: 99%

A single amino acid serves as an affinity switch between the receptor and the binding protein of corticotropin-releasing factor: Implications for the design of agonists and antagonists

Eckart

Jahn

Radulovic

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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In view of the observation that corticotropin-releasing factor (CRF) affects several brain functions through at least two subtypes of G protein-dependent receptors and a binding protein (CRFBP), we have developed synthetic strategies to provide enhanced binding specificity. Human͞rat CRF (h͞rCRF) and the CRF-like peptide sauvagine (Svg), differing in their affinities to CRFBP by two orders of magnitude, were used to identify the residues determining binding to CRFBP. By amino acid exchanges, it was found that Ala 22 of h͞rCRF was responsible for this peptide's high affinity to CRFBP, whereas Glu 21 located in the equivalent position of Svg prevented high affinity binding to CRFBP. Accordingly, [Glu 22 ]h͞rCRF was not bound with high affinity to CRFBP in contrast to [Ala 21 ]Svg, which exhibited such high affinity. Furthermore, the affinity of both peptides to either CRF receptor (CRFR) subtype was not reduced by these replacements, and their subtype preference was not changed. Thus, exchange of Ala and Glu and vice versa in positions 22 and 21 of h͞rCRF and Svg, respectively, serves as a switch discriminating between CRFBP and CRFR. On the basis of this switch function, development of new specific CRF agonists and antagonists is expected to be facilitated. One application was the modification of the CRF antagonist astressin (Ast), whose employment in animal experiments is limited by its low solubility in cerebrospinal fluid. Introduction of Glu residues into Ast generated with [Glu 11,16 ]Ast an acidic astressin, which efficiently antagonized in vivo the CRFR1-dependent reduction of locomotion induced by ovine CRF without detectable binding to CRFBP.

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“…In vitro assays indicate that AST is more potent for both CRH 1 and CRH 2 receptors than is another common CRH antagonist, αHelCRH, yet does not have its partial agonist properties (Brauns et al, 2001). However, in vivo studies in rats suggest that AST may be somewhat less potent in preventing some CRHand stress-induced and anxiety-related behaviors (Spina et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Mouse strain differences in the effects of corticotropin releasing hormone (CRH) on sleep and wakefulness

et al. 2008

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Corticotropin releasing hormone (CRH) plays a major role in central nervous system responses to stressors and has been implicated in stress-induced alterations in sleep. In the absence of stressors, CRH contributes to the regulation of spontaneous waking. We examined the effects of CRH and astressin (AST), a non-specific CRH antagonist, on wakefulness and sleep in two mouse strains with differential responsiveness to stress to determine whether CRH might also differentially affect undisturbed sleep and activity. Less reactive C57BL/6J (n=7) and high reactive BALB/cJ (n=7) male mice were implanted with a transmitter for determining sleep via telemetry and with a guide cannula aimed into a lateral ventricle. After recovery from surgery and habituation to handling, ICV microinjections of CRH (0.04, 0.2, and 0.4 μg), AST (0.1, 0.4, and 1.0 μg) or vehicle alone (pyrogenfree saline, 0.2 μl) were administered during the fourth h after lights on and sleep was recorded for the subsequent 8 h. Comparisons of wakefulness and sleep were conducted across conditions and across strains. In C57BL/6J mice, REM was significantly decreased after microinjections of CRH (0.2 μg) and CRH (0.4 μg), and NREM and total sleep were decreased after microinjections of CRH (0.4 μg ). CRH (0.4 μg) and AST did not significantly change wakefulness or sleep. In BALB/cJ mice, CRH (0.4 μg) increased wakefulness and decreased NREM, REM and total sleep. AST decreased active wakefulness and significantly increased REM at the low and high dosages. These findings demonstrate that CRH produces changes in arousal when given to otherwise undisturbed mice. Strain differences in the effects of CRH and AST may be linked to the relative responsiveness of C57BL/6J and BALB/cJ mice to stressors and to underlying differences in the CRH system.

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Pharmacological and chemical properties of astressin, antisauvagine-30 and α-helCRF: significance for behavioral experiments

Cited by 32 publications

References 39 publications

Modulation of multiple ethanol withdrawal-induced anxiety-like behavior by CRF and CRF1 receptors

Modulation of multiple ethanol withdrawal-induced anxiety-like behavior by CRF and CRF1 receptors

A single amino acid serves as an affinity switch between the receptor and the binding protein of corticotropin-releasing factor: Implications for the design of agonists and antagonists

Mouse strain differences in the effects of corticotropin releasing hormone (CRH) on sleep and wakefulness

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