Stimulus-evoked glutamate release is diminished by acute exposure to uranium in vitro

Uranium is used in civilian applications, in the manufacture of nuclear fuel, and by the military for munitions and armament, but little information is available on its neurotoxicity. Neurological dysfunctions have been observed after chronic exposure in both animals and humans, but the actions of acute exposure on amino acid neurotransmission have not been investigated. The following study was performed to examine the effects of uranyl ion (UO2+2) on hippocampal glutamatergic and GABAergic function as possible bases for the neurotoxicity and to assess the concentrations were applied to superfused hippocampal synaptosomes to permit estimation direct effects on the exocytotic process. Nominal UO2+2 of the metal's potency on endogenous transmitter release in the presence and absence of Ca+2. K+ -evoked glutamate release was diminished in the range of 10 nM-316 mu M UO2+2, resulting in an IC50 of 1.92 mu M. In contrast, the potency of UO2+2 to decrease stimulated GABA release was reduced, producing an IC50 approximate to 2.6 mM. In the absence of Ca+2 in the superfusion medium there was no systematic change in the magnitude of glutamate or GABA release, suggesting that UO2+2 does not possess Ca+2 -mimetic properties. The inhibitory potency of UO2+2 on glutamate release is similar to the potencies of other multivalent metal ions, suggesting by inference an action exerted on voltage-sensitive Ca+2 channels. The bases for the reduced potency to inhibit GABA release is not known, but differential sensitivity to other heavy metals has been reported for glutamate and GABA neurotransmission. These findings indicate a profile of neurotoxicity not unlike that of other metal ions, and indicate the importance of extending subsequent studies to chronic exposure models. (c) 2007 Elsevier Inc. All rights reserved.