Drugs acting at the strychnine-insensitive glycine receptor do not induce HSP-70 protein in the cingulate cortex.
The potential for compounds acting at the strychnine-insensitive glycine receptor to injure neurons was examined using induction of a 70 kDa heat shock protein (HSP-70) as a marker. HSP-70 was consistently detected in retrosplenial and cingulate cortices after MK-801 but not glycine drug treatment. Elsewhere in the cortex, mild diffuse HSP-70 immunoreactivity was detected following 7-chlorokynurenic acid. Following HA-966, intense hippocampal HSP-70 immunoreactivity was observed. These findings indicate that even after very high doses, drugs acting at the strychnine-insensitive glycine receptor are less likely to injure cingulate cortical neurons than other classes of NMDA antagonists.
Laboratory of Psychiatry and Neurology, SFVAMC/UCSF 94121.
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Berger
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Farrel
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Sharp
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Skolnick
D000596:Amino Acids / Q000494:pharmacology; D000598:Amino Acids, Cyclic; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000187:drug effects / Q000502:physiology*; D013331:Strychnine / Q000494:pharmacology*
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D006360:Heat-Shock Proteins; D011760:Pyrrolidinones; D018009:Receptors, Glycine; C023863:1-aminocyclopropane-1-carboxylic acid; D016291:Dizocilpine Maleate; C001369:1-hydroxy-3-amino-2-pyrrolidone; D007736:Kynurenic Acid; D013331:Strychnine; C057013:7-chlorokynurenic acid