NEURONAL CYTOTOXICITY OF INOSITOL HEXAKISPHOSPHATE (PHYTATE) IN THE RAT HIPPOCAMPUS

D-myo-Inositol hexakisphosphate (InsP6, phytate), a normal cellular co nstituent, was found to be toxic to neuronal perikarya when injected i nto the rat hippocampus. However, the extrinsic cholinergic innervatio n of the hippocampus (as estimated by staining for acetylcholinesteras e) was unaffected. Its potency as a toxin was approximately equal to t hat of the excitotoxin quinolinate. Other highly charged derivatives o f 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 a nother calcium chelator with a higher affinity for calcium, 2-bis(2-am inophenoxy)ethane-N,N,N',N'-tetra-acetic acid (BAPTA), produced only a very mild lesion. Thus, abnormal metabolism of InsP6 might possibly c ontribute to neuronal death in neurodegenerative diseases.