Browsing by Author "ARQUEROS, L"

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    L-GLUTAMIC ACID, A NEUROMODULATOR OF DOPAMINERGIC TRANSMISSION IN THE RAT CORPUS STRIATUM
    (1983) RUDOLPH, MI; ARQUEROS, L; BUSTOS, G
    A superfusion system was used to study the effects of neuroexcitatory amino acids upon spontaneous and depolarization-evoked release of exogenously taken up and newly synthesized [3H]dopamine by rat striatal slices. Neither L-glutamate nor other aminoacids such as L-aspartate and D-glutamate (5 .times. 10-5 M) modified the spontaneous release of exogenous [3H]dopamine from rat striatal slices. These neuroexcitatory aminoacids did potentiate spontaneous release of striatal [3H]dopamine newly synthesized from [3H]tyrosine. A different pattern of effects emerged when depolarization-evoked release of dopamine was studied. Only L-glutamate (5 .times. 10-6-1 .times. 10-4 M) potentiated dopamine release under these experimental conditions in a rather specific and stereoselective manner. Similar results were obtained regardless of whether depolarization-induced release of exogenous or newly synthesized [3H]dopamine was studied. The effect of L-glutamate on depolarization-induced release depended both upon the degree of neuronal depolarization and upon the presence of external Ca2+ in the superfusion medium and it was blocked by L-glutamate diethylester. This effect of L-glutamate seemed quite specific with regard to regional localization within the brain as it was only demonstrated in slices from striatum and not in slices from olfactory tubercle or hippocampus. It is suggested that during depolarization a Ca2+-dependent event occurs at the striatal membrane level which changes the sensitivity of the dopamine release process to neuroexcitatory aminoacids in such a way as to render it relatively more specific and steroselective towards L-glutamate stimulation. Evidently L-glutamic acid could play a role as a neuromodulator of dopaminergic transmission in the rat corpus striatum.
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    NICOTINE-INDUCED RELEASE OF CATECHOLAMINES FROM RAT HIPPOCAMPUS AND STRIATUM
    (1978) ARQUEROS, L; NAQUIRA, D; ZUNINO, E
    [3H]Catecholamine release from noradrenergic and dopaminergic neuron terminals of the CNS, induced by nicotine and K depolarization, was studied. Striatal and hippocampal slices of rat brain that incorporated [3H]catecholamines in previous incubations with the radioamines were superfused and stimulated by nicotine and high K. Nicotine produced a marked [3H]catecholamine release from these 2 brain areas, this effect being much greater in the striatum. The time course of radioactive efflux released by nicotine was different from that induced by high K and similar to that evoked by tyramine. Nicotine-induced released was dose dependent, inhibited by low temperature, independent of extracellular Ca and not inhibited by an excess of Mg. Studies with newly synthesized [3H]dopamine and [14C]urea suggested that nicotine acted on the storage vesicles. [3H]catecholamine release was continuous during prolonged nicotine stimulation, in contrast to the transient efflux induced by prolonged stimulation by K, and additive when the slices were superfused simultaneously with nicotine plus K. Previous nicotine superfusion did not modify the typical K release, and the response to nicotine was also not altered when the slices were exposed previously to high K. The mechanism of nicotine release of catecholamines from central catecholaminergic neuron terminals is discussed.
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    PHOSPHATIDYLINOSITOL-SPECIFIC PHOSPHOLIPASE-C SOLUBILIZED G2 ACETYLCHOLINESTERASE FROM PLASMA-MEMBRANES OF CHROMAFFIN CELLS
    (1989) PRIETO, AL; FUENTES, ME; ARQUEROS, L; INESTROSA, NC
    Using whole homogenates and defined subcellular fractions of bovine adrenal medulla, we investigated the properties of the dimeric G2 molecular form of acetylcholinesterase (AChE), its distribution, and the mode of attachment to chromaffin cells. Our studies indicate that a substantial fraction of the G2 form is specifically susceptible to solubilization by phosphatidylinositol-specific phospholipase C (PIPLC) from subcellular fractions enriched with plasma membrane fragments. The results suggest that the G2 form of AChE is anchored in the plasma membrane to a glycolipid domain that contains phosphatidylinositol. Since a Ca+2-dependent PIPLC has been previously described in chromaffin granules, it is possible that the adrenal AChE could be released by a system reminiscent of that involved in the case of the surface glycoprotein of Trypanosoma brucei.
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    RELEASE OF D-[H-3] ASPARTIC ACID FROM THE RAT STRIATUM - EFFECT OF VERATRIDINE-EVOKED DEPOLARIZATION, FRONTO-PARIETAL CORTEX ABLATION, AND STRIATAL LESIONS WITH KAINIC ACID
    (1985) ARQUEROS, L; ABARCA, J; BUSTOS, G
    The spontaneous and depolarization-evoked release of radiolabeled D-aspartic acid, previously taken up by rat striatal slices, was studied by using a superfusion system. Veratridine (10-50 .mu.M), electrical field stimulation (20 Hz, 1.0 V, 60 s), and K (53 mM) markedly potentiated the release of D-[3H]aspartate from striatal slices. The release of L-[3H]glutamate was also increased by veratridine, according to a pattern and time course of release similar to that of D-[3H]aspartate. The ratio of D-[3H]aspartic acid release evoked by veratridine over-spontaneous levels of release was much higher when compared to that of radiolabeled L-glutamate. Omission of Ca from the superfusion medium almost completely suppressed D-[3H]aspartate release evoked by veratridine or by electrical stimulation whereas high K+-evoked release of the [3H]amino acid was only slightly reduced. Increasing Mg2+ concentration of 12 mM in the superfusion medium did substantially block D-[3H]aspartate release induced by K+-depolarization. Tetrodotoxin (1 .mu.M), a blocker of voltage-dependent Na+ channels, totally abolished veratridine-evoked release of D-[3H]aspartate from striatal slices. Lesion studies showed that unilateral ablation of the frontoparietal cortex was accompanied by a significant decrease in the high-affinity uptake of striatal D-[3H]aspartate and by a large and parallel loss from striatal slices in D-[3H]aspartate release evoked by either veratridine or high K+. In contrast, unilateral injection of kainic acid into the striatum did not influence depolarization-evoked release of D-[3H]asparate from striatal slices. D-[3H]aspartic acid may be taken up preferentially and then released, in a Ca2+-dependent manner, by veratridine and electrical stimulation from nerve terminals belonging to the cortico-striatal pathway. Excitatory amino acids may act as neurotransmitters at the cortico-striatal nerve fibers.
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    SPECIFIC BINDING OF L-[H-3]-GLUTAMIC ACID TO RAT SUBSTANTIA-NIGRA SYNAPTIC-MEMBRANES
    (1986) FIEDLER, JL; ARQUEROS, L; BUSTOS, G
    The specific binding of L-[3H]-glutamic acid (GLU) was investigated in synaptic membranes from rat substantia nigra. L-[3H]-GLU binding to the membrane preparations occurred in a reversible and saturable way. The specific binding was stimulated by the presence of CaCl2 and was reduced by freezing and thawing the membranes. Scatchard analysis of the saturation isotherms yielded a non-linear plot suggesting that the binding reaction does not occur through a simple biomolecular association. Assuming non-interacting binding sites, a high (KD1, 139 nM; Bmax1, 3.5 pmoles/mg protein) and a low (KD2, 667 nM; Bmax2, 15.1 pmoles/mg protein) affinity L-[3H]-GLU binding site were obtained. The kinetics of dissociation of bound L-[3H]-GLU was biphasic; the respective dissociation rate constant (k-1) being 0.20 min-1 and 0.013 min-1. A series of amino acid receptor agonists and antagonists were tested as inhibitors of L-[3H]-GLU specific binding. Quisqualic acid, L-GLU and D-.alpha.-aminoadipate (D-.alpha.-AA) were the most potent inhibitors. DL-2-amino-4-phosphonobutyrate (APB), N-Methyl-D-aspartate (NMDA) and D-GLU were moderate inhibitors, whereas diaminopimelic acid (DAPA) and glutamate diethyl ester (GDEE) exhibited the lowest relative potency. Kainic acid (KA), .gamma.-aminobutyric acid (GABA) and bicuculline were not able to modify at any concentration used the specific binding of L-[3H]-GLU. These data demonstrate the presence of specific GLU binding sites in synaptic structures at substantia nigra level and support the idea that excitatory amino acids may play a role in synaptic transmission in this brain region.