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Biomedical subjects

D D Wheeler

Publications and source records attributed to D D Wheeler.

At least 37 records · Page 2Linked to original sources
PubMed1983

Aging of the high affinity GABA transporter in synaptosomes from the hypothalamus of the rat.

Initial velocity of GABA uptake in hypothalamic synaptosomes has been measured in aged animals as a function of both sodium and GABA concentration and compared to previous studies in young animals. The data give good fit to the model found previously to give minimal best fit to control data. Thus it appears that aging has not resulted in a change in fundamental mechanism by which carrier, sodium, and GABA interact in the process of transport. However, changes were found in the constants which quantitate the model. As a consequence, there is a reduction in transport capability in the aged animals which is particularly apparent at the higher sodium concentrations. The best fit constants were used along with the rate equation from the model to calculate several kinetic parameters which are useful in comparing transport mechanisms. In the physiological range of sodium concentration, those kinetic parameters related to maximal transport capabilities declined with age, while apparent carrier affinities increased with age. Similar results were found in previous studies of GABA (Wheeler, 1982) and glutamic acid (Wheeler, 1980a) transport in cortical synaptosomes.

Aging↗
PubMed1982

Effect of castration on the high affinity glutamate transporter in rat hypothalamic and cortical synaptosomes.

High affinity transport of glutamic acid has been studied in cortical and hypothalamic synaptosomes from castrated male rats and compared to normal controls. For hypothalamic synaptosomes, both initial velocity of uptake of Va (apparent maximal velocity) were found to be about one-third lower in the castrated animals. Kt (glutamate concentration giving Va/2), however, was reduced by only 5%. Initial velocity of uptake in cortical synaptosomes was measured as a function of both sodium and glutamate concentration. Reductions in uptake subsequent to castration were found to be much less for cortical synaptosomes (2-15%) than for hypothalamic synaptosomes. Fit of these data to various models for the sodium dependence of transport resulted in the same minimal best fit model as that found for control animals. Thus castration does not alter the fundamental nature of the mechanism by which carrier, sodium and glutamate interact in the process of transport. However, quantitative changes were found to occur, as reflected in the best fit constants. These constants were used along with the rate equation for the minimal best fit model to calculate certain parameters which were then used to delineate the quantitative changes in the transporter following castration. A neuroregulatory role for glutamate in gonadotropin secretion has been recently proposed; the present study now provides additional information on the relationship between reproductive function and one aspect of glutamatergic synaptic function, namely, the high affinity transport system.

Animals↗
PubMed1982

Aging of membrane transport mechanisms in the central nervous system. GABA transport in rat cortical synaptosomes.

A kinetic study of sodium dependent GABA transport has been made in synaptosomes from 30-month old Long-Evans rats and compared to results from 2-month old animals. Initial velocity of uptake was measured as a function of both sodium and GABA concentration, and these data were than fitted to the model which was found to give best fit for the 2-month data. An excellent fit was also obtained for the 30-month data. Thus there has been no change with age in the fundamental mechanism by which carrier, sodium, and GABA interact in the process of transport. However, quantitative changes were found to occur with age both in initial velocity of uptake and in those constants which quantitate the model. The rate equation for the model was utilized along with the best fit constants to define and calculate certain parameters which were then used to quantitatively compare the transport mechanism in young and aged animals.

Aging↗
PubMed1982

Increase in K+ and alpha-AIB active transport in CHO cells after low [K+] treatment.

We have studied the effects of prolonged incubation in low [K+] medium (approximately 0.3 mM) on both K+ and amino acid transport in Chinese hamster ovary (CHO) cells. When incubated in low [K+] medium, CHO cells redressed partially the loss of intracellular K+ after 12 h. After 24 h of incubation, both the activity of Na+-K+-ATPase in crude homogenates, and the transport capacity (Vmax) for ouabain-sensitive (i.e., active) K+ influx approximately doubled. The magnitude of the ouabain-insensitive (i.e., passive) K+ influx decreased by 50%. Thus the regulatory response involves an apparent increase in Na+-K+ pump and a decrease in K+ leak. The transport capacity for the nonmetabolized amino acid, alpha-aminoisobutyric acid (alpha-AIB), also increased after 24 h in low [K+] medium. The Vmax for the Na+-dependent (i.e., active) alpha-AIB influx increased by about 150%, and the magnitude of the Na+-independent influx increased by 20-40%. These changes in alpha-AIB transport result in a twofold greater capacity to accumulate this amino acid. Thus the regulation of K+ and alpha-AIB transport systems appears to be linked and possible mechanisms of this linkage are discussed.

Aminoisobutyric Acids↗
PubMed1981

Sodium dependence of high affinity glutamic acid transport in cortical synaptosomes--a comparison of Long-Evans and Sprague-Dawley rats.

The sodium dependence of high affinity glutamic acid transport has been studied in cortical synaptosomes from Sprague-Dawley rats and compared to previous studies with Long-Evans rats. Initial velocity of uptake was measured as a function of both glutamate and sodium concentration, and the data fitted to the rate equations for the same set of models that was utilized in the Long-Evans studies. The minimal best-fit model was found to be identical to that found previously for Long-Evans animals. Thus there are no fundamental differences in the basis of the sodium dependence of high affinity glutamate transport between the two groups. However, since the constants describing the best fit model are different for the two groups of animals, there are quantitative differences in the transport mechanism between the two groups. The rate equation for the minimal best-fit model permits certain functions to be defined in terms of dissociation and translocation constants, substrate, sodium, and total carrier concentrations. These functions were calculated and then utilized to demonstrate the quantitative differences in the transport mechanism in the two groups.

Animals↗
PubMed1980

Glutamic acid transport in cortical synaptosomes from essential fatty acid deficient rats.

the sodium dependence of the high-affinity transport of glutamic acid in rat brain synaptosomes has been studied in animals maintained on a diet deficient in essential fatty acids (EFAD), and the results compared to similar studies with animals on a normal diet. Although the data give best fit to the same kinetic model as for control data, there are differences in the constants that describe the model. Except at low sodium concentrations, uptake is lower for the EFAD gorup. As a consequence of the differences in constants for the two groups, there are quantitative differences in the transport mechanism. The rate equation for the best fit model has been utilized to define certain functions in terms of dissociation and translocation constants, glutamate, sodium, and total carrier concentrations. These functions were calculated and utilized to compare the transport mechanism for the two groups. Although there are differences between these functions for control and EFAD animals, these differences are small and therefore of doubtful physiological significance.

Animals↗
PubMed1980

Sodium dependence of GABA transport in rat hypothalamic synaptosomes.

The sodium dependence of gamma-aminobutyric acid (GABA) uptake has been studied in rat hypothalamic synaptosomes, and the results compared to previous studies in cortical synaptosomes. Initial velocity of GABA uptake was measured as a function of both GABA and sodium concentration, and these data were fitted to the rate equation for each of several plausible models. The minimal best-fit model was found to be identical to that for cortical synaptosomes. However, the constants which quantitate the model were found to differ for hypothalamus and cortex. As a result, uptake at any combination of [Na] and [G] in hypothalamic synaptosomes is approximately double that in cortical synaptosomes. The rate equation for the minimal best-fit model was utilized to define and compute certain parameters which are useful in comparing transport mechanisms (Vmax, Va, Kt, Jm, and k Na). In all cases, differences were found between hypothalamus and cortex.

Animals↗
PubMed1979

Effects of polarizing currents and repetitive stimulation on the uptake of amino acids by peripheral nerve.

The effects of polarizing currents and repetitive stimulation on the uptake of representative amino acids have been studied in peripheral nerve. Glutamic acid, lysine, pheylalanine, and GABA were chosen for study as representatives of different carrier-mediated transport mechanisms. Depolarizing currents inhibited uptakes of glutamic acid, lysine, and GABA; maximum inhibitions were 56.1%, 20.0%, and 16.7%, respectively. Pheylalanine uptake was not inhibited by polarizing currents under any experimental conditions. Only glutamic acid uptake was inhibited by hyperpolarizing current, with a maximum inhibition of 43.9%. Stimulation had no significant effect on uptake of lysine, phenylalanine, or GABA but was found to potentiate uptake of glutamic acid by 12%.

Amino Acids↗
PubMed1979

Uptake of 2-deoxy-D-glucose by cortical synaptosomes from the Long-Evans rat.

Uptake of 2-deoxy-D-glucose (2-DG) has been studied in synaptosomes from the Long-Evans rat. Although there are some differences, the results are generally similar to those reported for Sprague--Dawley rats. Both D-glucose and 2-DG are taken up by the same carrier, since D-glucose was found to inhibit uptake of 2-DG. Uptake is highly dependent on a source of metabolic energy, since incubation at 0 degrees C completely eliminated uptake, while 10(-3) M 2,4-dinitrophenol (DNP) inhibited uptake by 76.5%. Uptake has also been measured as a function of both 2-DG and sodium concentration and the data fitted to a model. Sodium is found to inhibit uptake. A model assuming noncompetitive inhibition by sodium gives best fit to the data. Thus both Kt and apparent Vm are dependent on the sodium concentration. Although these effects are small, Kt increases with [Na], while apparent Vm declines.

Animals↗
PubMed1979

A model of GABA transport by cortical synaptosomes from the Long-Evans rat.

The initial velocity of uptake of GABA by cortical synaptosomes from the Long-Evans rat has been measured as a function of both sodium and GABA concentration. These data were then fitted to the rate equation for each of several possible models, and the models giving least error were identified. Although one cannot unequivocally distinguish between two of the models on the basis of the goodness of fit, deductions based on the fits of subsets of the models point to one of the two models, The major predictions from this model are as follows: 1) Uptake of GABA is totally sodium-dependent. 2) Although plots of 1/v versus 1/[Na]2 are nonlinear, the coupling ratio for transport (Na/GABA) is 2. 3) For transport to take place, the order of combination with carrier must be Na, Na, GABA. 4) Maximal velocity will occur only at infinite Na and GABA concentrations. 5) There is a sigmoidal relationship between apparent maximal velocity (Va) and [Na]. 6) Kt, the [GABA] that gives a velocity equal to Va/2, rises and then falls as [Na] is increased from zero, passing through a maximum at 33.52 mM [Na]. 7) The relationship between initial velocity and [Na] is sigmoidal. 8) Jm, rate of uptake with infinite [Na], is hyperbolically related to [GABA]; Jm approaches Vmax as [GABA] becomes very large. 9) kappa Na, the [Na] giving a velocity equal to Jm/2, declines rapidly from 10(-7) M to 10(-5)M GABA, but is essentially constant at 10(-4)M above. 10) One GABA molecule is translocated per carrier molecule. The model is consistent with observations in the literature concerning the effects of sodium on the kinetics of transport.

Animals↗
PubMed1977

Locus of interference on the Stroop test.

On the Stroop test subjects are presented with a random sequence of color names printed in random colors of ink. They are asked to go through the list twice, once reading the words aloud and once naming the ink colors. In this experiment 36 college students were also asked to go through the lists using their fingers to make push button responses. With verbal responses naming the ink colors took nearly twice as long as reading the words, thus replicating the usual Stroop test results. With either the left hand or the right there was no difference between the time required by the subjects to respond to the words and to the ink colors. The disappearance of the Stroop effect with finger responses suggests strongly that the interference normally shown on the Stroop test occurs primarily in the processing of the verbal response.

Color Perception↗