Metyrapone, an inhibitor of corticosterone synthesis, blocks the kainic acid-induced expression of HSP 70.
It is shown in the present study that metyrapone (100 mg/kg), an inhibitor of corticosterone synthesis, given twice, 30 min before and 6 h after kainic acid (10 mg/kg) administration, blocks the kainic acid-evoked induction of heat shock proteins 72 kDa (HSP 70). Specifically, it was observed that metyrapone completely prevented kainic acid-induced appearance of HSP 70 in the rat amygdala, habenula, parietal cortex, and significantly decreased the number of HSP 70-positive neurons in the CA1, CA3, and CA4 subregions of hippocampus. The reduction in HSP 70 induction was paralleled by a complete prevention of the kainic acid-induced rise in the circulating corticosterone level by metyrapone; however, in applied doses metyrapone evoked slight enhancement of blood corticosterone. Despite the fact that metyrapone blocked/attenuated the kainic acid-evoked induction of HSP 70, its administration did not affect the behavioral effects of kainic acid, regarded as "limbic status epilepticus." It is concluded that the blockade of corticosterone synthesis might have neuroprotective effects in the pathological states associated with the overstimulation of glutamatergic receptors.
Czyrak
A
A
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.czyrak@if-pan.krakow.pl
Fijał
K
K
Maćkowiak
M
M
Zajaczkowski
W
W
Wedzony
K
K
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003345:Corticosterone / Q000037:antagonists & inhibitors* / Q000097:blood; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects* / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D008797:Metyrapone / Q000494:pharmacology* / Q000627:therapeutic use; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D018690:Excitatory Amino Acid Agonists; D018840:HSP70 Heat-Shock Proteins; D007608:Kainic Acid; D003345:Corticosterone; D008797:Metyrapone