Premium
Modification of Brain Guanine Nucleotide‐Binding Regulatory Proteins by Tryptamine‐4,5‐Dione, a Neurotoxic Derivative of Serotonin
Author(s) -
Fishman Jordan B.,
Rubins Jeffrey B.,
Chen JinChung,
Dickey Burton F.,
Volicer Ladislav
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb03440.x
Subject(s) - tryptamine , guanine , guanosine , chemistry , serotonin , gtp' , guanosine diphosphate , biochemistry , nucleotide , g protein , stereochemistry , receptor , enzyme , gene
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 G i and G o to [ 3 H]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 G i and G o (∼40,000). The binding of [ 35 S]guanosine‐5′‐ O ‐(3‐thiotriphosphate) ([ 35 S]GTP‐γ‐S) to G i and G o and pertussis toxin‐catalyzed [ 32 P]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.