Effects of glutaminase inhibition on release of endogenous glutamic acid.
The effects of four inhibitors of glutamine hydrolysis on synaptosomes derived from several regions of the brain were studied. The calcium-specific release of endogenous glutamic acid was determined in the presence of varying concentrations of 6-diazo-5-oxo-norleucine (DON), N-ethyl-maleimide (NEM), 2-chloroadenosine (2-CA) or haloperidol. Both DON and NEM reduced the calcium-specific release in a concentration-dependent manner, equally in all regions tested. 2-Chloroadenosine also decreased release and the effect was most evident in the amygdala. As reported earlier, haloperidol blocked release of glutamic acid only in the amygdala. In synaptosomes from the amygdala, both DON and NEM failed to affect the calcium-specific release of aminobutyric acid (GABA), glycine or serotonin at concentrations which reduced release of glutamate by 50%; NEM, but not DON, elevated the release of dopamine. Dopamine itself affected neither the release of glutamate nor its blockade by haloperidol even in extremely large concentrations.
D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000679:Amygdala / Q000502:physiology; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D003980:Diazooxonorleucine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D005972:Glutaminase / Q000037:antagonists & inhibitors*; D005998:Glycine / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D005971:Glutamates; D003980:Diazooxonorleucine; D015762:2-Chloroadenosine; D001224:Aspartic Acid; D012701:Serotonin; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005972:Glutaminase; D006220:Haloperidol; D000241:Adenosine; D005998:Glycine; D004298:Dopamine