Neuronal cytotoxicity of inositol hexakisphosphate (phytate) in the rat hippocampus.
D-myo-Inositol hexakisphosphate (InsP6, phytate), a normal cellular constituent, was found to be toxic to neuronal perikarya when injected into the rat hippocampus. However, the extrinsic cholinergic innervation of the hippocampus (as estimated by staining for acetylcholinesterase) was unaffected. Its potency as a toxin was approximately equal to that of the excitotoxin quinolinate. Other highly charged derivatives of inositol (inositol hexakissulphate, inositol monophosphate) were not toxic. The cytotoxicity of InsP6 was not due to a high osmolality, or to seizure-induced lesions, but was reduced by calcium. Nevertheless, the toxicity was not due to chelation of brain calcium by InsP6, as another calcium chelator with a higher affinity for calcium, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), produced only a very mild lesion. Thus, abnormal metabolism of InsP6 might possibly contribute to neuronal death in neurodegenerative diseases.
Lees
G J
GJ
Department of Psychiatry and Behavioural Science, School of Medicine, University of Auckland, New Zealand. gj.lees@auckland.ac.nz
Leong
W
W
D000818:Animals; D001665:Binding Sites; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity; D009474:Neurons / Q000187:drug effects*; D010833:Phytic Acid / Q000633:toxicity*; D017378:Quinolinic Acid / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
D002614:Chelating Agents; D018690:Excitatory Amino Acid Agonists; D004533:Egtazic Acid; D016202:N-Methylaspartate; D010833:Phytic Acid; D017378:Quinolinic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid