Modification of Brain Guanine Nucleotide‐Binding Regulatory Proteins by Tryptamine‐4,5‐Dione, a Neurotoxic Derivative of Serotonin

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Abstract
We have recently characterized a novel oxidation product of serotonin (5‐hydroxytryptamine, 5‐HT), tryptamine‐4,5‐dione, which increases 5‐HT efflux from striatum and hippocampus and causes selective neuronal death. Exposure of striatal synaptosomes or the major brain guanine nucleotide‐binding regulatory proteins Gi and Go to [3H]tryptamine‐4,5‐dione resulted in the radiolabeling of a major band with an apparent molecular mass equivalent to that of the α subunits of Gi and Go (∼40,000). The binding of [35S]guanosine‐5′‐O‐(3‐thiotriphosphate) ([35S]GTP‐γ‐S) to Gi and Go and pertussis toxin‐catalyzed [32P]ADP‐ribosylation of the G protein α subunits were both inhibited in a dose‐dependent manner by tryptamine‐4,5‐dione. Thus, neurotoxins such as tryptamine‐4,5‐dione may exert their effects through specific interactions with G proteins.