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M E Sandoval

Publications and source records attributed to M E Sandoval.

12 recordsLinked to original sources
PubMed1985

Sodium-dependent, calmodulin-dependent transmitter release from synaptosomes.

The baseline efflux of gamma-amino[2,3-3H]butyric acid ([3H]GABA) and [3H]dopamine ([3H]DA) from caudate synaptosomes was greatly enhanced by the sodium-ionophore monensin; this stimulatory effect of monensin on transmitter release was markedly inhibited by trifluoperazine (TFP), a potent calmodulin antagonist. TFP also decreased the depolarization-induced, calcium-dependent release of [3H]GABA and this effect was unrelated to the calcium-flux across the plasma membrane since TFP also inhibited the release of GABA elicited by the calcium-ionophore A23187. Our data indicate that transmitter release induced by both increased intraterminal sodium levels and by the calcium entry into the nerve endings during depolarization might be mediated by calmodulin-dependent processes.

Animals↗
PubMed1984

Serotonin uptake and release from rat cerebellum in vitro.

Serotonin (5-HT) uptake and release were analyzed in cerebellar fractions. Cerebellar, P2 fractions and molecular layer homogenates are able to accumulate exogenous 5-HT through an Na-dependent, high-affinity transport system. Molecular layer 5-HT uptake, however, was totally dependent upon Na+, whereas the accumulation of the amine by P2 fractions from whole cerebellum was also carried out by an Na-independent transport system. Ca++-dependent release of recently accumulated 5-HT was observed in both P2 fractions and molecular layer homogenates when depolarizing conditions were used. This release was blocked by ruthenium red and Mg++, two inhibitors of the Ca++ entry to the nerve endings induced by depolarization. The molecular layer homogenates released twice as much 5-HT as did cerebellar P2 fractions, indicating that serotoninergic boutons in the cerebellar cortex might be located in the molecular layer. Our results suggest that 5-HT might play a transmitter role in the cerebellum.

Animals↗
PubMed1984

High affinity uptake and Ca2+-dependent release of glutamic acid in the developing cerebellum.

This study was undertaken in order to evaluate the postulated role of glutamic acid as the neurotransmitter for the parallel fibers of the cerebellar cortex. We studied the Ca2+-dependent release and the high affinity uptake of glutamic acid in the developing cerebellum. The Ca2+-dependent release of glutamic acid from cerebellar molecular layer during development closely follows the time course of parallel fibers synaptogenesis. Little glutamic acid release was observed at 15 days, then it increased to the adult values at the 21st postnatal day. In the rat the bulk of synapses of the parallel fibers appear between the 15th and the 21st postnatal days, the time at which the nerve terminals of the climbing fibers, the other excitatory input to the Purkinje cells, are already developed. An enhanced Na+-dependent, high affinity uptake of glutamic acid was observed in the developing cerebellum relative to the adult rat. That this higher accumulation of glutamic acid is not related to a releasable pool is suggested by the fact that an enhanced glutamic acid, Ca2+-dependent release relative to the adult was not observed. These results support the view that glutamic acid is the transmitter for the cerebellar parallel fibers.

Animals↗
PubMed1980

Studies on the relationship between Ca2+ efflux from mitochondria and the release of amino acid neurotransmitters.

It is known that transmitter release depends upon the entry of calcium ions into the synaptic terminal. Mitochondria have been suggested to play a key role on the regulation of intracellular Ca2+ concentration, thereby influencing transmitter liberation and synaptic transmission. Here we report the stimulatory effect of DNP and FCCP, uncouplers of oxidative phosphorylation, and quinidine, known to induce muscle contractures and increase Ca2+ efflux from muscle mitochondria, on both [14C]glutamic acid and [3H]GABA unstimulated release from synaptosomes and loss of 45Ca2+ from preloaded whole brain mitochondria. Results showed that the spontaneous efflux of non-putative neurotransmitters, leucine and alpha-aminoisobutyric acid, was less affected or not stimulated at all, under similar experimental conditions. Data suggest that calcium ions released from mitochondria are able to trigger neurotransmitter release.

Animals↗
PubMed1980

Sodium-dependent efflux of [3H]GABA from synaptosomes probably related to mitochondrial calcium mobilization.

It has been suggested that mitochondria might modify transmitter release through the control of intracellular Ca2+ levels. Treatments known to inhibit Ca2+ retention by mitochondria lead to an increased transmitter liberation in the absence of external Ca2+, both at the frog neuromuscular junction and from isolated nerve endings. Sodium ions stimulate Ca2+ efflux from mitochondria isolated from excitable tissues. In the present study, the effect of increasing internal Na+ levels on [3H]gamma-aminobutyric acid ([3H]GABA) release from isolated nerve endings is reported. Results show that the efflux of [3H]GABA from prelabeled synaptosomes is stimulated by ouabain, veratrine, gramicidin D, and K+-free medium, which increase the internal sodium concentration. This effect was not observed when Na+ was omitted from the incubation medium and it was independent of external Ca2+, the experiments having been performed in a Ca2+-free, EGTA-containing medium. Since preincubation of synaptosomes with 2,4-diaminobutyric acid did not prevent the stimulatory effect of increased internal Na+ levels on [3H]GABA efflux, it appears to be unrelated to an enhanced activity of the outward carrier-mediated GABA transport. These results suggest that the augmented release of [3H]GABA may be due to an increased Ca2+ efflux from mitochondria elicited by the accumulation of Na+ at the nerve endings.

Animals↗
PubMed1975

GABA metabolism and cerebral protein synthesis.

Glutamate decarboxylase (GAD) activity and [14C)leucine incorporation into brain protein in vivo were measured in mice injected with L-glutamic acid-gamma-hydrazide and 60 min later with pyridoxal-5'-phosphate; this combined treatment produces a decrease in GAD activity and an increase in GABA levels. Under such conditions, protein synthesis was inhibited to the same extent as GAD activity. A parellelism between the decrease in GAD activity and that in protein synthesis was also observed in brain cortex slices treated with GAD inhibitors. This treatment did not affect leucine incorporation into protein in liver slices. The results support the previously suggested hypothesis that a certain pool of GABA may have a role in the regulation of protein synthesis in brain, and further suggest that the synthesis of GABA may be more important in this respect than its total concentration.

Aminobutyrates↗