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Notes: Abstract— The influx and efflux of [3H]GABA were investigated in synaptosomes. Two efflux components were detected. The first, termed spontaneous efflux, was not affected by the external sodium chloride concentration. The second, termed GABA-stimulated efflux, was observed when low levels of GABA were added to the incubation medium and was found to require external sodium chloride. The rate of spontaneous efflux at 0°C was about 37 per cent of the rate at 27°C but both GABA-stimulated efflux and GABA influx were completely inhibited at 0°C. The stimulation of efflux by external GABA followed simple Michaelis–Menten kinetics with respect to external GABA. The concentration of external GABA required for half-maximal stimulation was 4·9 ± 1·4 μm and the Vmax for efflux was 1·0 ± 0·6 nmol. min-1.mg-1 of protein. A similar stimulation of efflux was observed with GABA analogue l-2,4-diamino-butyric acid which is a competitive inhibitor of influx. The concentration of external l-2,4-diaminobutyric acid required for half-maximal stimulation of efflux was 51 ± 12 μm and the Vmax for efflux was 0·8 ± 0·5 nmol.min-1.mg-1 of protein. Since the sodium-dependency, temperature sensitivity, and kinetic properties of the GABA-stimulated efflux system were similar to the influx system, GABA-stimulated efflux was attributed to carrier-mediated exchange diffusion. Measurement of efflux and influx in the same preparation showed there was a net efflux when total fluxes were considered and that the exchange ratio (influx to GABA-stimulated efflux) was 0·9 when carrier-mediated fluxes were considered. The effect of the temperature of the fluid used to rinse synaptosomes collected on filters in influx experiments was investigated. There was no detectable difference in measured values of influx between samples rinsed with cold fluid (0°C) and warm fluid (27°C). The endogenous GABA content of synaptosomes was found to be 20·3 ± 2·5 nmol GABA per mg of protein. From this value, the cytoplasmic concentration of GABA in synaptosomes was estimated to be a maximum of 40 mm. About 5 per cent of total cerebral cortical GABA was found in the synaptosomal fraction.

Notes: The kinetics of transport of gamma-aminobutyric acid [2,3-3H] by synaptosomes from rat brain was studied by means of a rapid filtration technique. The rate of uptake was proportional to the protein concentration over the range 0.05—0.2 mg of synaptosomal protein per ml. Although apparent allosteric kinetics were observed with sodium, transport followed simple saturation kinetics with respect to GABA and no heterotropic, cooperative effects of GABA on sodium on kinetics were observed. A minimum of three interacting sodium sites is suggested the basis of Hill plots of the sodium data. Both the apparent Km and Vmax for GABA were functions of the sodium ion concentration but the effect of sodium was considerably greater on Vmax than on the apparent Km The Vmax for GABA was 1.1 ± 0.5 nmol.min−1 mg−1 of protein at 95 mm sodium and decreased to 12 per Cent of this value at 19 mm sodium. The apparent Km for GABA increased from 4.0 ± 1.0 μm at 95 mm sodium to 8.4 ± 2.0 μm at 19 mm sodium. Potassium was a noncompetitive inhibitor with respect to GABA and did not affect the apparent cooperativity observed with sodium. These findings are discussed in terms of models of GABA transport.

Notes: Abstract— The initial rate of uptake of [2,3-3H]gamma-aminobutyric acid by rat brain synaptosomes was studied under incubation conditions in which GABA metabolism was minimal. The presence of both sodium and potassium in the incubation medium was essential for sustained uptake. Uptake proceeded for a short period of time in the absence of potassium and then ceased. No uptake was observed when sodium chloride was completely replaced with sucrose or choline chloride. The sodium-dependence curve for GABA uptake was markedly sigmoid. The sigmoid character of the curve was not attributable to a lag phase in uptake at low sodium concentrations. Calcium strongly stimulated the initial rate of uptake at low sodium concentrations but had little effect at sodium concentrations above 100 mm and was not able to support uptake in the absence of sodium. The sigmoid character of thesodium-dependence curve was completely eliminated by 20 mm calcium ion. Magnesium and phosphate had little effect on the initial rate of GABA uptake.

Notes: Many so-called ‘technology transfer’ programs are based on the belief that the process is essentially one of communication rather than of innovation. As such, the designers and managers of such programs concern themselves with questions of how to transfer technology after it is already developed, rather than how to develop or adapt technology so that it is transferable. The net result, we believe, has been a very poor showing and a very low level of effectiveness. To design a successful transfer program one must develop a view of the flow of technology in an integrated innovation process, and this paper concludes with the presentation of a highly significant flow model in which the critical aspect is constant assessment of the non-technological factors during the entire course of the innovation cycle–including those related to marketing, regulations, capital and human resources.