ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
In primary cultures of mouse cerebral cortex neurons, sulphur-containing excitatory amino acids (SAAs; namely, L-cysteine sulphinate, L-cysteate, L-homocysteine sulphinate, L-homocysteate, S-sulphocysteine) at concentrations ranging from 0.1 μM to 1 mM evoked a saturable release of -γ-[3H] aminobutyric acid ([3H] GABA) in the absence of any other depolarizing agent. All SAAs exhibited essentially similar potency (EC50), 100–150 nM) in releasing [3H] GABA although a variable profile of maximal stimulatory effect was observed when compared with basal release. The intracellular accumulation of the lipophilic cation, [3H] tetraphenylphosphonium, was significantly reduced in the presence of all SAAs, thus verifying a depolarization of the neuronal plasma membrane. SAA-stimulated release of [3H] GABA was shown to comprise two distinct components, calcium-dependent and calcium-independent, which occur after activation of N-methyl-B-aspartate (NMDA) and non-NMDA receptors. Thus, all SAA-evoked responses were antagonized by the selective, competitive NMDA-receptor antagonist, 3-[(±)-2-carboxypiperazin-4-yl] propyl-1-phosphonic acid (IC50range, 〉50 μM) and the non-NMDA-receptor antagonist, 6, 7-dinitroquinoxalinedione (IC50 range, 5–50 nM). Removal of magnesium ions from the superfusion medium caused a significant potentiation of SAA-evoked responses without having any effect on basal levels of [3H] GABA efflux, a result consistent with an involvement of NMDA-receptor activation. Calcium-independent release (i.e., that release remaining in the presence of 1 mM cobalt ions) was a distinct component but of smaller magnitude. Using 500 pMexcitatory amino acid agonist concentrations, this component of release was (1) markedly attenuated by 15 fiMSKF-89976-A, a non- transportable inhibitor of theGABA carrier, and (2) abolished when choline ions replaced sodium ions in the superfusion medium or when in the presence of excitatory amino acid receptor antagonists. These observations are dearly consistent with a receptor-mediated, depolarization-induced reversal of the GABA carrier.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1471-4159.1991.tb08305.x
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