SUMMARY1. The effects of graded concentrations of caffeine on the Na efflux were investigated. External application of 10 mm caffeine usually caused a biphasic response, viz, a fall, followed by a rise in the Na efflux. 1 and 5 mm caffeine usually caused stimulation. Only the stimulator phase of this response depended on the presence of external Ca2+.2. Internal application of 100 mm~caffeine caused a small rise in the Na efflux, the magnitude of which was independent of external Ca2+ and comparable to that obtained with external application of 1 mm caffeine. This action, however, could be greatly augmented by pre-treating the fibre with x 10-5 M ouabain.3. The rise in Na efflux caused by external application of 10 mmc affeine could be greatly augmented by pre-treating the fibre with 5 x IO--M ouabain. The observed stimulatory response was biphasic, more so in the absence of external Ca2+. Restoration of external Ca2+ following the onset of the second stimulatory phase resulted in further rise of the Na efflux. Measurements of the Na efflux during treatment with graded concentrations of ouabain and 10 mm~caffeine showed that the rate coefficient for Na efflux varied with the ouabain concentration in the range 10-8_10-4 M. Measurements of the ouabain-insensitive Na efflux before and during treatment with 10 mmw caffeine in bathing media containing varying concentrations of Ca, disclosed the existence of two Ca2+_ thresholds, one in the 0-2-5 mm range and the other in the 12-5-15 mm range.4. Comparisons were made between the effects on the Na efflux of * Permanent address: Department of Biological Sciences, University-of Lancaster, Bailrigg, Lancaster LAI 4YQ, England.1-2 2~~E. EDWARD BITTAR AND OTHERS 10 mm caffeine followed by external acidification, and external acidification, followed by 10 mm caffeine. The magnitude of the response of the ouabaininsensitive Na efflux to external acidification before treatment with 10 mm caffeine was greater than that found when external acidification followed external application of the alkaloid. It also was considerably greater than that of the response to external application of 10 mm caffeine before external acidification.5. External application of 10 mm procaine prevented 10 mmw caffeine from stimulating the Na efflux, and from inducing contractures. Internal application of 100 mm-EGTA reduced the response of the Na efflux to 10 mmw caffeine, and also prevented the fibre from contracting. External application of 10-4m diphenylhydantoin reduced the response of the Na efflux to 10 mmw caffeine but failed to prevent the development of contractures.6. Internal application of 0-05 m-cGMP, cAMP or its dibutyryl derivative caused a large rise in the Na efflux. The magnitude of the effects observed in ouabain-poisoned fibres was often greater than that in unpoisoned fibres. Internal application of 2-5 units/ml. phosphodiesterase beforehand failed to reduce the magnitude of the stimulatory response to injected cyclic nucleotides. Injected phosphodiesterase also failed to reduce th...
Paired fed and fasted rats were subjected to the standard shock procedure consisting of a combination of tail bleeding and heart puncture with an intervening recovery period of 90 minutes. Mortality rates in the two groups were similar but the survival times were shortened in the fasted group. Following tail bleeding all animals mobilized glucose into the blood stream and developed severe hyperglycemia. In those individuals in either group which ultimately died, the blood sugar levels were further reduced following heart puncture; the rates of glucose loss were inversely proportional to survival time; the results were terminal hypoglycemias and near exhaustion of liver glycogen. In contrast, the survivors in either group, examined 4 hours after heart puncture, were found to be hyperglycemic and engaged in glycogen neogenesis. It is concluded that the ultimate death or survival of an animal in hemorrhagic shock is independent of its initial glucose reserves, but seems somehow to be related to its ability to maintain itself in a hyperglycemic state.
Some studies were made of the influence of dietary molybdenum on intestinal alkaline phosphatase activity. It was observed that after one week on the experimental regimen 5 rats receiving 1200 p.p.m. molybdenum had significantly less (P< 0.01) intestinal phosphatase activity than 5 controls. Control and toxic values were 16.58 t 1.64 and 4.46 t 0.73 pM phosphate released/30'/mg protein respectively. Because of this rapid and pronounced effect, the influence of sodium molybdate on the intestinal phosphatase assay system was tried. Molybdate concentrations up to M had no influence on a semi-purified preparation of intestinal phosphatase. At 31 molybdate, a 20% inhibition of activity was observed. This is in agreement with experiments on liver preparations( 10) and suggests that the decrease in activity observed in toxicity is probably a reflection of altered synthesis of the enzyme rather than a direct influence of the mineral on the enzyme assay system.Summary. 1. High levels of dietary molybdenum did not alter ability of rat to acetylate p-aminobenzoic acid or to conjugate benzoic acid with glycine. 2. A depression of food intake and growth was evident within 24 hours after addition of 0.12% molybdenum to the 'diet. 3. Liver alkaline phosphatase activity was significantly increased in mulybdenum-toxic rats whereas the activities of the kidney and intestinal alkaline phosphatases were significantly reduced.
A procedure consisting of a combination of tail bleeding and heart puncture has allowed the controlled withdrawal of predetermined amounts of blood from rats. Within a narrow bleeding range of 3.9–4.0 vol. % body weight the mortality rate has been found to rise sharply from 20–70%. Survival or death do not seem to be associated with any significant changes in the fluid contents of the small intestine despite the marked hemorrhagic discoloration seen at autopsy. The removal of 4.1 (or more) vol. % body weight of blood results in a mortality rate of 80–85% with no deaths occurring beyond 4 hours. Observations made before and after death suggest that the rats die from irreversible hemorrhagic shock. The method is applicable to experiments involving 10–20 animals at a time.
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