Dithiotreitol specifically inhibits metabotropic responses of glutamate and depolarizing agents in rat brain synaptoneurosomes.
Dithiotreitol (DTT), a sulfhydryl reducing agent inhibits in a dose-dependent manner the inositol phosphates (IPs) accumulation responses evoked by glutamate and potassium without affecting that of carbachol in rat forebrain synaptoneurosomes. Furthermore, DTT neither provokes a depolarization of the membrane, nor increases the internal calcium concentration. Depolarization and internal calcium rise are known to stimulate IPs production. Moreover, DTT does not modify the depolarizing effect and the calcium rise elicited by glutamate and potassium. In addition, the antioxidant compounds 2-aminoethylisothiouronium bromide (AET) and ascorbic acid have no effect on the basal and stimulated IPs accumulation. Thus, it is concluded that: (1) two distinct transduction pathways exist, one stimulated by glutamate and depolarizing agents and the other one by cholinergic agonists; (2) DTT produces its inhibition by reducing disulfide bridges likely at the level of proteins of the phosphoinositide transduction mechanism.
INSERM U-254 Hôpital St Charles, Montpellier, France.
M
M
Vignes
J
J
Guiramand
I
I
Sassetti
M
M
Recasens
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D004229:Dithiothreitol / Q000494:pharmacology*; D016257:Fura-2; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology*; D016548:Prosencephalon / Q000378:metabolism*; D051381:Rats; D013050:Spectrometry, Fluorescence; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
D000975:Antioxidants; D005971:Glutamates; D007295:Inositol Phosphates; D018698:Glutamic Acid; D007294:Inositol; D002217:Carbachol; D011188:Potassium; D002118:Calcium; D004229:Dithiothreitol; D016257:Fura-2