PMID: 8939445Oct 1, 1996Paper

Cadmium rapidly and irreversibly blocks presynaptic phospholipase C-linked metabotropic glutamate receptors

Neurochemistry International
M VignesM Récasens

Abstract

Calcium ions (Cd2+) inhibit inositol phosphate (IP) formation elicited by glutamate (GLU) or K+ ions, without affecting carbachol (Carb)-induced IP response in 8-day-old rat forebrain synaptoneurosomes and synaptosomes. On the contrary, Cd2+ was almost ineffective in blocking GLU- and K(+)-responses in hippocampal neurones in culture. The mechanism of Cd2+ inhibition was thus examined in synaptoneurosomes. Extensive washing of synaptoneurosomes pretreated for 1, 5, 15, or 30 min by 100 microM Cd2+ did not modify the inhibitory effect of Cd2+ on GLU-, K(+)- and A23187-evoked IP formation or its lack of effect on Carb response. The later addition of a high affinity Cd2+ chelator (100 microM), N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) also did not reverse the inhibitory effect. TPEN, however, penetrates into synaptoneurosomes and efficiently displaces Cd2+ from the Fura-2-Cd2+ complex as shown by Fura-2 fluorescence recordings. TPEN is not easily removed from the intracellular space, as demonstrated by its ability to still block Cd(2+)-induced Fura-2 fluorescence increase after extensive washing. Pretreatment of synaptoneurosomes by this chelator did not prevent Cd2+ inhibition of GLU-induced IP formation. These da...Continue Reading

References

Mar 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·F NicolettiE Costa
Apr 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·S WeissJ Bockaert
Sep 1, 1994·Trends in Pharmacological Sciences·J Watkins, G Collingridge
Feb 1, 1994·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·E MayatM Récasens
Apr 1, 1993·The European Journal of Neuroscience·M VignesM Récasens

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