Modification of brain guanine nucleotide-binding regulatory proteins by tryptamine-4,5-dione, a neurotoxic derivative of serotonin.
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 alpha subunits of Gi and Go (approximately 40,000). The binding of [35S]guanosine-5'-O-(3-thiotriphosphate) ([35S]GTP-gamma-S) to Gi and Go and pertussis toxin-catalyzed [32P]ADP-ribosylation of the G protein alpha 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.
Fishman
J B
JB
Department of Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01655.
Rubins
J B
JB
Chen
J C
JC
Dickey
B F
BF
Volicer
L
L
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002384:Catalysis; D005033:Ethylmaleimide / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000037:antagonists & inhibitors / Q000378:metabolism; D045563:Indolequinones; D009498:Neurotoxins / Q000494:pharmacology*; D037342:Pertussis Toxin; D012701:Serotonin / Q000378:metabolism; D014363:Tryptamines / Q000378:metabolism* / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D045563:Indolequinones; D009498:Neurotoxins; D014363:Tryptamines; D010566:Virulence Factors, Bordetella; C060213:tryptamine-4,5-dione; D000246:Adenosine Diphosphate Ribose; D012701:Serotonin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D005033:Ethylmaleimide