Metyrapone, an inhibitor of corticosterone synthesis, blocks the kainic acid-induced expression of HSP 70

Czyrak, A; Fijał, Katarzyna; Maćkowiak, Marzena; Zaja̧czkowski, Wojciech M.; Wędzony, K

doi:10.1002/1098-2396(200011)38:2<144::aid-syn5>3.0.co;2-f

Cited by 7 publications

(5 citation statements)

References 46 publications

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“…The actions of opioids on the HPA axis are believed to be mediated, directly or indirectly, by the release of corticotropin-releasing factor and the ability to stimulate the HPA axis can be blocked by opioid antagonists (Pechnick 1993). Interestingly, metyrapone, an inhibitor of corticosterone synthesis, has been shown to block the kainate-induced expression of Hsp70 (Czyrak et al 2000). It could be likely, that the upregulation of the Hsp70 expression in the paraventricular nucleus of the hypothalamus in this study may reflect some effects of morphine on the endocrine system.…”

Section: Discussionmentioning

confidence: 65%

Rapid, transient, and dose-dependent expression of Hsp70 messenger RNA in the rat brain after morphine treatment

Ammon-Treiber

Grecksch²,

Stumm³

et al. 2004

Cell Stress Chaper

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Induction of Hsp70 in the brain has been reported after intake of drugs of abuse like amphetamine and lysergic acid diethylamide. In this investigation, gene expression of Hsp70 and other heat shock genes in the rat brain was studied in response to morphine. Twenty milligrams per kilogram morphine intraperitoneally resulted in a marked induction of Hsp70 messenger RNA (mRNA) expression in the frontal cortex with a maximum increase of 13.2-fold after 2 hours. A moderate increase of Hsp27 mRNA expression (6.7-fold) could be observed after 4 hours, whereas mRNA expression of Hsp90 and of the constitutive Hsc70 did not exceed a mean factor of 1.8-fold during the 24 hours interval. The increase in Hsp70 mRNA was dose dependent, showing a significant elevation after doses ranging from 10 to 50 mg/kg morphine. In situ hybridization revealed enhanced Hsp70 mRNA expression mainly in cortical areas, in the hippocampus, in the paraventricular and supraoptic nuclei of the hypothalamus, in the locus coeruleus, as well in the pineal body. The double in situ hybridization technique revealed increased Hsp70 mRNA expression mainly in VGLUT1-positive neurons and to a lesser extent in olig1-positive oligodendroglia. Immunohistochemistry revealed a marked increase of Hsp70 protein in neuronal cells and blood vessels after 12 hours. In contrast to animal experiments, morphine did not increase Hsp70 mRNA expression in vitro in micro-opioid receptor (MOR1)-expressing human embryonic kidney 293 cells, suggesting no direct MOR1-mediated cellular effect. To exclude a body temperature-related morphine effect on Hsp70 mRNA expression, the temperature was recorded. Five to 20 mg/kg resulted in hyperthermia (maximum 40.6 degrees), whereas a high dose (50 mg/kg) that produced the highest mRNA induction, showed a clear hypothermia (minimum 37.2 degrees C). These findings argue against the possibility that Hsp70 induction by morphine is caused by its effect on body temperature. It may be speculated that increased expression of Hsp70 after morphine application protects brain structures against potentially hazardous effects of opiates.

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Section: Discussionmentioning

confidence: 65%

Rapid, transient, and dose-dependent expression of Hsp70 messenger RNA in the rat brain after morphine treatment

Ammon-Treiber

Grecksch²,

Stumm³

et al. 2004

Cell Stress Chaper

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“…Induction of the cellular stress response in the hippocampus following status epilepticus Heat-shock proteins are a family of molecular chaperones that are induced in the CNS following a range of stresses, such as hyperthermia, ischemia, and kainic acid-induced SE (Koroshetz and Bonventre 1994;Brown 2007). Hsps have been used as markers of neuronal injury (Gonzalez et al 1989;Lowenstein et al 1990;Armstrong et al 1996;Czyrak et al 2000). In this study, the profile of Hsps following pilocarpine-induced SE was determined by western blotting.…”

Section: Resultsmentioning

confidence: 99%

Extracellular matrix protein SC1/hevin in the hippocampus following pilocarpine‐induced status epilepticus

Lively

Brown

2008

Journal of Neurochemistry

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Pilocarpine‐induced status epilepticus (SE) mimics many features of temporal lobe epilepsy and is a useful model to study neural changes that result from prolonged seizure activity. In this study, distribution of the anti‐adhesive extracellular matrix protein SC1 was examined in the rat hippocampus following SE. Western blotting showed decreased levels of SC1 protein in the week following SE. Immunohistochemistry demonstrated that the decrease in overall SC1 protein levels was reflected by a reduction of SC1 signal in granule cells of the dentate gyrus. Interestingly, levels of SC1 protein in neurons of the seizure‐resistant CA2 sector of the hippocampus did not change throughout the seizure time course. However, at 1 day post‐SE, a subset of neurons of the hippocampal CA1, CA3, and hilar regions, which are noted for extensive neuronal degeneration after SE, exhibited a transient increase in SC1 signal. Neurons exhibiting enhanced SC1 signal were not detected at 7 days post‐SE. The cellular stress response was also examined. A prominent induction of heat‐shock protein (Hsp70) and Hsp27 was detected following SE, while levels of constitutively expressed Hsp40, Hsp90, Hsp110, and Hsc70 showed little change at the time points examined. The subset of neurons that demonstrated a transient increase in SC1 colocalized with the cellular stress marker Hsp70, the degeneration marker Fluoro‐Jade B, and the neuron activity marker activity‐regulated cytoskeleton‐associated protein (Arc). Taken together, these findings suggest that SC1 may be a component of the ‘matrix response’ involved in remodeling events associated with neuronal degeneration following neural injury.

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“…Metyrapone inhibits the 11-hydroxylase enzyme, by which it also inhibits corticosterone and aldosterone production process via 11-deoxycorticosterone. Inhibition of the 11-hydroxylase enzyme restrains the formation of cortisol from deoxycortisol (Schoneshofer et al, 1980;Burtis and Ashwood, 1999;Czyrak et al, 2000). This information based on the literature review and our results, shows that endogenous cortisol creates analgesia via an indirect mechanism.…”

Section: Discussionmentioning

confidence: 98%

Effects of epinephrine and cortisol on the analgesic activity of metyrosine in rats

Albayrak¹,

Sağlam

Yıldırım

et al. 2011

Arch. Pharm. Res.

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Some endogenous hormones (epinephrine and cortisol) can change an individual's pain threshold. Propranolol is a non-selective β adrenergic receptor blocker which antagonises the anti-inflammatory effect of non-steroidal anti-inflammatory drugs via the β1 and β2 adrenergic receptors. The roles of epinephrine and cortisol were investigated in the analgesic activity of metyrosine in rats with reduced epinephrine levels induced by metyrosine. Pain threshold measurement was performed using an analgesimeter with different doses and the single or combined usage of metyrosine, prednisolone, metyrapone and propranolol in rats. Epinephrine and corticosterone levels were measured by high-performance liquid chromatography in metyrosineadministered rats. Metyrosine reduces the epinephrine levels without affecting the corticosterone levels, thereby creating an analgesic effect. It was determined that prednisolone did not have an analgesic effect in rats with normal epinephrine levels, but its analgesic activity increased with a parallel decrease in the epinephrine levels. Similarly, the combined use of prednisolone and metyrosine provided a stronger analgesic effect than that rendered by metyrosine alone. The strongest analgesic effect, however, was observed in the group of rats with the lowest epinephrine level in whom the metyrosine + prednisolone combination was administered. The findings of this study may be useful in severe pain cases in which the available analgesics are unable to relieve the individual's pain.

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Metyrapone, an inhibitor of corticosterone synthesis, blocks the kainic acid-induced expression of HSP 70

Cited by 7 publications

References 46 publications

Rapid, transient, and dose-dependent expression of Hsp70 messenger RNA in the rat brain after morphine treatment

Rapid, transient, and dose-dependent expression of Hsp70 messenger RNA in the rat brain after morphine treatment

Extracellular matrix protein SC1/hevin in the hippocampus following pilocarpine‐induced status epilepticus

Effects of epinephrine and cortisol on the analgesic activity of metyrosine in rats

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