Facultad de Ciencias Médicas

About: Facultad de Ciencias Médicas is a based out in . It is known for research contribution in the topics: Population & Fatty acid. The organization has 4833 authors who have published 3708 publications receiving 38112 citations.

Subcellular distribution of the enzymes of the glutamic acid, glutamine and gamma-aminobutyric acid cycles in rat brain.

Abstract: RECENT studies have stressed the important physiological role of certain amino acids in the brain. Analytical determinations revealed high concentrations of glutamic and aspartic acids as well as of glutamine and N-acetylaspartate. y-Aminobutyric acid (GABA), is especially interesting, not only because of its high concentration, but also because of its exclusive presence in the CNS, particularly in grey matter. Numerous biochemical studies have been dedicated to the metabolic interrelationships existing among this group of amino acids and the glycolytic and tricarboxylic cycles, as well as with the mechanism of ammonia removal in brain. Some of these amino acids may serve as anions, making up for part of the inorganic anion deficit, or as important substrates in intermediary metabolism. Experimental observations have shown that these amino acids may have different physiological actions. Both glutamic and aspartic acids have a powerful excitatory action. On the contrary, GABA has a general depressant action on different neuronal responses while glutamine and N-acetylaspartic acid have no effect. It has been suggested that some of these amino acids are important in maintaining the normal excitability of neuronal membranes acting in a rather unspecific way, while others have suggested a synaptic role for them (see CURTIS, PHILLIS and WATKINS, 1959, 1960; CURTIS and WATKINS, 1960; FLOREY, 1964). The function of this group of amino acids seems to be related to the complex structure of the CNS and the existence of numerous compartments and metabolic pools. With radioisotope experiments it has been found that only a small fraction of the total glutamate is rapidly interchanged, while the rest remains rather inactive (BERL, TAKACAKI and PURPURA, 1961b). Similarly, only a small fraction of GABA appears to be active (BERL, LAJTHA and WAELSCH, 1961~). Furthermore some of these amino acids apparently can exchange across cell membranes, and this exchange is accelerated by stimulation of nerve cells (LUXORO, 1960).

Isolation of synaptic vesicles and structural organization of the acetylcholine system within brain nerve endings

Abstract: THE DISCOVERY of synaptic vesicles as the most significative component of nerve endings (DE ROBERTIS and BENNETT, 1954, 1955) led to the suggestion that they could be the site of storage and synthesis of transmitter substances. Since then this concept has become associated with the notion of a “quantized” release of acetylcholine at the neuromuscular junction (DEL CASTILLO and KATZ, 1956). At the same time several indirect indications of the role of these vesicles in synaptic transmission were demonstrated (DE ROBERTIS, 1959). The stimulation of some cholinergic terminals by DE ROBERTIS and VAZ FERREIRA (1957) and subsequent electronmicroscope observations suggested that within the endings a balance exists between the formation and release of synaptic vesicles, related to the frequency of stimulation. The isolation of such a subcellular component remained as the most direct approach to the elucidation of the chemical nature and physiological significance of synaptic vesicles. An approach to such a goal was made independently by DE ROBERTIS et al. (1960, 1961a) and GRAY and WHITTAKER (1960) with the demonstration that the so-called mitochondrial fraction of the brain contained a considerable number of isolated nerve endings in addition to free mitochondria and myelin. In our first paper we reported an attempt to isolate synaptic vesicles by disrupting the endings mechanically and subfractionating the microsomes in a continuous gradient. However the vesicles isolated in one of the four microsomal fractions were not as regular in size as the true synaptic ones. At that time we postulated that: “the further purification of intact synaptic terminals may provide a good starting point for the isolation of pure synaptic vesicles”. We also stated that : “when this is done, the synaptic vesicles will be probably found in one of the submicrosomal fractions”. More recently a technique was developed in our laboratory which allows the subfractionation of the mitochondrial fraction (Mit)? into five separated layers which in order of increased density are essentially composed of: A, myelin; B, fragments of endings and membranes; C , cholinergic nerve endings; D, non-cholinergic nerve endings; and E, free mitochondria (see methods and electronmicrographs in DE ROBERTIS et al., 1962a). The two subfractions C and D of nerve endings provided an excellent material for the isolation of synaptic vesicles. However it was observed