Depressive effects of lipid peroxides mediated via a purine receptor. Effect of lipid peroxide on the cortical synaptosomal GTPase activity.
A circadian rhythm of lipid peroxides (LPO) in mouse whole brain was observed with a negative correlation between LPO levels in cerebral cortex and the locomotor activity of mice. Intraperitoneal administration of t-butyl hydroperoxide (BPO) to mice decreased spontaneous locomotor activity in a dose-dependent manner, and the effect was competitively antagonized by caffeine, suggesting a similar receptor. Cumene peroxide (CPO), BPO and known depressants such as phenobarbital and NaBr all stimulated GTPase activity in rat cerebral cortex synaptosomes. In contrast, stimulants, such as caffeine and amphetamine, inhibited GTPase activity. Using fresh and aged synaptosomes which differed markedly in endogenous LPO levels, it appeared as if the LPO competitively inhibited inosine-induced GTPase activity, suggesting that the receptor of LPO is the same as that of inosine. From these results, it is concluded that LPO in brain act as depressants whose activity can be competitively antagonized by caffeine, and that the effects of LPO are mediated through a purine receptor.
Hasegawa
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Department of Community Health Science, Saga Medical School, Nabeshima, Japan.
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D002940:Circadian Rhythm; D015536:Down-Regulation / Q000187:drug effects; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D008054:Lipid Peroxides / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects; D051379:Mice; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011983:Receptors, Purinergic / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects
D008054:Lipid Peroxides; D011983:Receptors, Purinergic; D002110:Caffeine; D020558:GTP Phosphohydrolases; D000241:Adenosine; D010634:Phenobarbital