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Biomedical subjects

M G Wyllie

Publications and source records attributed to M G Wyllie.

At least 55 records · Page 3Linked to original sources
PubMed1983

Critical assessment of noradrenaline uptake in synaptosomal preparations.

Synaptosomes and other subcellular organelles were prepared from rat brain using a vertical rotor. The preparation time was reduced by up to 60% compared to conventional techniques. Uptake of [3H]-(-)-noradrenaline into subcellular fractions was characterized. The characteristics of this uptake were dependent on the subcellular composition and anatomical origin. Various methods of correction for energy independent processes were compared, but only sodium ion removal from the medium selectively inhibited the energy dependent uptake mechanism. Kinetic analysis of data revealed that high and low affinity uptake systems were dependent on the fraction under analysis. Noradrenaline uptake was not exclusively localised in noradrenergic terminals. Selective inhibitors of the noradrenaline uptake process (tricyclic antidepressants) inhibited energy dependent uptake completely only in purified synaptosomes prepared from cortex. In whole brain synaptosomal fractions, noradrenaline was partially accumulated into dopaminergic neurones; this uptake process was not inhibited by tricyclic antidepressants.

Absorption↗
PubMed1983

Influence of thyroid hormone on diet-induced thermogenesis in the rat.

Energy balance and brown adipose tissue (BAT) metabolism were studied in rats maintained on stock or 'cafeteria' diet, and injected with either saline or triiodothyronine (T3, 10 micrograms/100 g b.wt./d) for 14 d. Cafeteria-fed rats showed large increases in metabolizable energy intake, energy expenditure and BAT mass, Na+, K+-ATpase activity and mitochondrial GDP binding. In stock fed rats, T3 also stimulated energy intake, metabolic rate and BAT mass and Na+, K+-ATPase activity, but did not affect GDP binding. Hyperthyroidism potentiated the effects of cafeteria feeding on energy expenditure and BAT mass, but BAT Na+, K+-ATPase activity was only slightly higher than that of the euthyroid cafeteria rats, and GDP binding was similar for both groups. These results confirm the involvement of BAT in diet-induced thermogenesis and show that this is potentiated by hyperthyroidism. The data also suggest that thyroid thermogenesis may result, at least partly, from stimulation of BAT.

Adipose Tissue, Brown↗
PubMed1983

Influence of chronic administration of ciclazindol on energy balance and brown adipose tissue in adult 'cafeteria'-fed rats.

The effects of chronic oral administration of ciclazindol on energy balance and brown adipose tissue (BAT) activity were studied in adult rats maintained on a palatable cafeteria diet. Treatment with 1 mg ciclazindol/kg/day produced small, but not significant, reductions in body energy gain and increases in BAT mass and protein content. Administration of 3.4 and 11 mg/kg/day of ciclazindol depressed weight gain and caused a substantial (42%) reduction in body energy gain. These effects were partly due to a lower food intake, but also resulted from a marked decrease in energetic efficiency. Rats treated with 3.4 and 11 mg/kg/day of the drug showed significant increases in BAT protein content, Na+, K+-ATPase activity and mitochondrial proton conductance, assessed from GDP-binding capacity. These results show that the reduced body weight produced by ciclazindol is due to a lower energetic efficiency, which is associated with activation of BAT, and also a depressed food intake.

Adipose Tissue, Brown↗
PubMed1982

Dopaminergic mechanisms in diet-induced thermogenesis and brown adipose tissue metabolism.

The role of dopamine (DA) in diet-induced thermogenesis was examined. DA was found in, and released from the sympathetic nerves supplying brown adipose tissue. However, the release of DA was only approximately 10% of that of noradrenaline. No significant re-uptake of DA was observed. Hyperphagic, cafeteria-fed rats exhibited higher rates of resting oxygen consumption (VO2) and increased DA release and turnover in brown adipose tissue relative to control animals. Pimozide completely abolished the difference in VO2 between the two groups and DA (0.5 mg . kg-1 s.c.) stimulated VO2 in control and cafeteria animals.

Adipose Tissue, Brown↗
PubMed1982

Resolution of monoamine uptake into binding and translocation components.

Kinetic analysis of the energy-independent accumulation of noradrenaline as determined by either sodium omission or osmotic lysis, revealed two components: a) a low affinity system which may represent extraneuronal uptake and b) a high affinity component which was characteristic of the physiological re-uptake process. A comparison between intact and lysed synaptosomes suggested that this high affinity system may represent binding to the carrier protein which was no dependent on external sodium. Qualitatively similar results were observed for serotonin. The results are discussed in relation to models of neuronal re-uptake.

Animals↗
PubMed1982

Catecholamine and thyroid hormone influence on brown fat Na+, K+-ATPase activity and thermogenesis in the rat.

Resting oxygen consumption (VO2) before and after injection of noradrenaline (NA), and plasma triiodothyronine levels were elevated in hyperthyroid and hyperphagic cafeteria fed rats, but were reduced in 4d-fasted and hypothyroid animals compared to controls. Refeeding fasted rats with a single carbohydrate meal caused all of these parameters to increase towards control levels. In vivo turnover, and in vitro release of NA brown adipose tissue (BAT) was elevated in cafeteria fed rats but remained unaltered in other groups and levels and uptake of NA in BAT were similar for all rats. Basal and NA stimulated Na+,K+-ATPase activity in BAT was increased in cafeteria and hyperthyroid rats and reduced in fasted and hypothyroid animals compared to control and refed groups. A highly significant correlation (r = 0.977), (P less than 0.001), found between the in vitro activity of this enzyme and resting VO2 in all rats, indicates that BAT Na+,K+-ATPase may be involved in the thermogenic responses to diet, catecholamines and thyroid hormones.

Adipose Tissue, Brown↗
PubMed1981

Sympathetic mechanisms in diet-induced thermogenesis: modification by ciclazindol and anorectic drugs.

1 The sympathetic noradrenergic activation of brown adipose tissue and the biochemical mechanisms involved in diet-induced thermogenesis were studied in rats. 2 A close correlation was found between brown adipose tissue Na+, K+-adenosinetriphosphatase (Na+, K+-ATPase) activity in vitro and in vivo measurements of resting oxygen consumption (VO2). The effects of noradrenaline on in vitro NA+, K+-ATPase activity in brown adipose tissue and in vivo VO2 could be mimicked by a variety of agents. These included beta-adrenoceptor agonists and agents known to induce the release of noradrenaline or inhibit the noradrenaline uptake process. The pharmacological evidence suggests that dopaminergic mechanisms may also be involved in the control of thermogenesis. 3 Amphetamine did not increase VO2 in rats without causing associated increases in locomotor activity. Ciclazindol at doses of 3-30 mg/kg intraperitoneally increased VO2 but did not appear to increase locomotor activity or evoke any other signs of CNS stimulation including lengthening of time to sleep onset or stereotypy. Separation of metabolic and CNS effects occurred only at the lowest dose of mazindol used (0.3 mg/kg i.p.). These results are probably a reflection of (a) the relative abilities of these drugs to inhibit brain and brown adipose noradrenaline uptake processes and (b) the relatively high accumulation of ciclazindol in brown adipose. 4 Of the drugs tested, only ciclazindol was a more potent inhibitor of the noradrenaline uptake system in brown adipose tissue (BAT) than in brain. Kinetic analysis also revealed that the actions of ciclazindol on the NA uptake system and Na+, K+-ATPase in BAT differed from those of mazindol. 5 These findings suggest that ciclazindol may produce an energy wasting effect in rodents without causing overt CNS stimulation; the implications of these findings in terms of human obesity are discussed.

Adipose Tissue, Brown↗
PubMed1981

The rapid preparation of synaptosomes, using a vertical rotor.

A rapid method for the preparation of isolated nerve terminals (synaptosomes) is described. The material, prepared using a vertical rotor, is compared biochemically with material prepared by conventional techniques. The synaptosomes possess many characteristics expected of isolated nerve terminals, including noradrenaline release and transport against a concentration gradient.

Animals↗
PubMed1980

The relationship between nerve terminal adenosine triphosphatases and neurotransmitter release: as determined by the use of antidepressant and other CNS-active drugs.

1 The role of adenosine triphosphatases (ATPases) in neurotransmitter release was studied using nerve terminals (synaptosomes) prepared from rat cerebral cortex as a model. 2 Amitriptyline, nortriptyline, protriptyline, desipramine and imipramine were found to inhibit ATPases at concentrations of 10(-5) M and above. The drugs inhibited both the basal and electrically evoked release of acetylcholine (ACh) and noradrenaline (NA) at concentrations of 10(-4) M and above. 3 At low concentrations of antidepressants (10(-8) and 10(-7) M) release of NA was enhanced but there was no effect on ACh release. 4 Other drugs which inhibit Na+, K+-ATPase increase basal NA release as did drugs which inhibited vesicular MG2+-ATPase. 5 A model is proposed suggesting that transmitter release/re-uptake depends on (1) active Na+, K+-ATPase at the presynaptic membrane and (2) an active synaptic vesicular MG2+-ATPase.

Acetylcholine↗
PubMed1980

Stimulation and inhibition of synaptosome ATPases by noradrenaline. The involvement of cytoplasmic factor.

The activity of Na+, K+-ATPase was determined in synaptosomes and in pellets, (containing membranes, mitochondria and vesicles) and cytoplasm prepared from synaptosomes from rat cerebral cortex. The activity of the pellets was more than two fold higher than that of the synaptosomes or of their components and adding back the cytoplasm reduced the activity of the pellets. Noradrenaline did not affect the activity of the pellets but increased that of the synaptosomes in a dose-dependent fashion. It inhibited the activity of the membranes. Results indicate that synaptosomal Na+, K+-ATPase activity is low because of a factor in the cytoplasm and this factor is not present in synaptosome pellets. NA antagonises the activity of the factor.

Animals↗
PubMed1979

An investigation into the roles of synaptic vesicular Mg++-ATPase in neurotransmitter release, using benzhydryl piperazines.

A series of benzhydryl piperazines was found to inhibit synaptic vesicular Mg++-ATPase. These compounds were also found to increase basal and evoked release of noradrenaline from synaptosomes. A comparison was made between the concentrations effective in inhibiting the enzyme and promoting noradrenaline release. In general, as the degree of Mg++-ATPase inhibition increased, noradrenaline release was increased. The relevance of these findings to a possible role of Mg++-ATPase in noradrenaline release is discussed.

Acetylcholine↗