The influence of chronic hyper- and hypothyroidism on the uptake and retention of tritiated noradrenaline ([3-H]NA) and on the endogenous noradrenaline (NA) content of various adrenergically innervated tissues was studied in thyroidectomized and sham-operated euthyroid rats. Half of the thyroidectomized rats were treated daily with thyroxine (25 mug/kg) for 3 or 12 weeks to simulate a condition of chronic hyperthyroidism, while the other half was left untreated to form a hypothyroid group. The body weight and the heart rate of each rat were measured at the end of each experiment, and in addition, at the end of the 3 week experiment, the oxygen consumption and the plasma thyroxine levels were measured to confirm the thyroid state of the animals. At the end of both experiments, each animal was given an intravenous injection of [3-H]NA and the [3-H]NA and the total endogenous NA content of the heart and various other adrenergically innervated tissues were measured on a timed schedule, to compare the initial accumulations and the rates of efflux of [3-H]NA under different thyroid states. Although the hyperthyroid rats had higher heart rates and heart weights, they were not significantly different from the euthyroid controls with respect to their body weights, tissue NA content, or accumulation and efflux rates of [3-H]NA. In contrast, the hypothyroid rats showed significantly lower heart and other tissue weights, but higher tissue concentrations of NA and rates of efflux of [3-H]NA than the euthyroid group. In the hypothyroid state, the NA turnover appeared to be increased as the [3-H]NA efflux rate was increased from the hearts and adrenal glands. There were no significant differences between the results of the 3 week and the 12 week experiments and no evidence that prolongation of the hyperthyroid state gave different results from those found by other workers who used much shorter treatment periods and larger doses of thyroxine to develop hyperthyroidism.

Noradrenaline (NA) uptake was measured in the anococcygeus by two methods: quantitative fluorescence microscopy and radioactive tracer techniques. A pharmacological analysis of the contribution of adrenergic nerve, smooth muscle, and nonspecific binding to collagen and basement membrane was attempted by studying the effects of desmethylimipramine and phenoxybenzamine on uptake. The importance of metabolic degradation in the process of NA accumulation was estimated by examining the effect of the combined use of iproniazid to inhibit monoamine oxidase and of β-thujaplicin to inhibit catechol O-methyltransferase.The results suggest that NA accumulation in this tissue at concentrations below 2 × 10−6 g/ml was almost entirely due to uptake into adrenergic nerves and to nonspecific binding. At higher concentrations of NA, above 2 × 10−6 g/ml, uptake into the smooth muscle cells began to contribute increasingly to the total accumulation. Inhibition of the metabolic enzymes increased the fluorescence of smooth muscle incubated with high concentrations of NA, confirming that only at those high concentrations was there any intracellular accumulation of NA and suggesting that the NA taken up by these smooth muscle cells is normally almost completely metabolized. Incubation with the inhibitors of catecholamine metabolism, and also with phenoxybenzamine, reduced both the fluorescence in the adrenergic nerve terminals and the accumulation of tritiated compounds by the whole tissue. Possible explanations for this observation are discussed.In the radioactive experiments 14C-sorbitol was used to measure the extracellular space (ECS). The ECS appeared to be a two-compartment system, a large, fast-filling and a small, slow-filling compartment. Electron micrographs suggest a possible basis for these two compartments in the large spaces between muscle bundles and the very narrow clefts between the cells in individual bundles. Quantitative estimates of the magnitude of these two spaces from electron micrographs are not incompatible with this.

The hypothesis that the limiting factor controlling the noradrenaline-releasing activity of a sympathomimetic amine is the ability of the nerve ending to take up the amine, i.e. the affinity of the amine for the postulated amine carrier in the sympathetic nerve ending, was tested on perfused rat hearts labelled with tritiated noradrenaline (NA). Experiments were done to determine whether cocaine and desmethylimipramine (DMI) would block the releasing action of sympathomimetic amines (SMA) and to determine whether the ranking order of the releasing activity of a series of SMA corresponds to the order of affinity for the amine carrier as reported by Iversen. The releasing activity of NA was found to be a saturable process, reaching a maximum rate estimated to be 2.6% of the amount present in the heart per minute. In addition, cocaine and DMI competitively blocked the releasing activity of infused NA, adrenaline, and dopamine, but this inhibition could be overcome by increasing the dose of the SMA. The ranking order of releasing activity of this series of amines was l-noradrenaline, dopamine, l-adrenaline, p-tyramine, d-noradrenaline, d-adrenaline, l-isoproterenol, phenylethylamine, d-isoproterenol, which was approximately the same as their order of affinity for the amine carrier. Our results indicate that uptake by a membrane carrier is probably the limiting factor in the releasing activity of SMA which are catechols and have a β-OH group. However, those amines studied which do not have these structural properties, i.e. dopamine, tyramine, and phenylethylamine, are further limited in their releasing activity, possibly owing to a less rapid exchange at the binding site on the storage granule.

The agriculturist in the Province of Ontario has annually to suffer gjreat loss from the depredations of two classes of enemies, both individually insignificant, but, by reason of their numbers, very formidable. These are insects and small rodents, chief among the latter being rats and all the animals usually classed as micfe.It is very difficult to make anything like a correct estimate of the average damage inflicted upon the farmer by these little animals, but every man engaged in farming knows by sad experience that he continually suffers from their work. The enormous amount of grain they destroy, and the young trees girdled and killed by them are visible to everyone ; but the creatures themselves, owing to their nocturnal habits and secretive lives, are comparatively seldom seen. Their enormous increase and consequent capacity for serious mischief is, of course, owing to the fact that man has interfered seriously with the balance of nature, and has thoughtlessly, perhaps, destroyed the principal natural enemies of these creatures.Man himself is almost powerless to stop their ravages to any very great extent.The constant exercise of his ingenuity in trapping, and so forth, results in very little and occupies his time to no purpose. The natural enemies of these animals are gifted with special faculties for their destruction, and so are able to cope with them. Chief among the enemies of this class of farm pests, and the only ones we shall consider now, are the birds of prey. These birds are wonderfully provided by nature with the means to fulfil their part in maintaining the correct balance between the small rodents and the vegetable kingdom. They are in a manner nature's police, and if not destroyed by man would so keep down the numbers of these small four-footed thieves that their plundering would be scarcely noticeable.Our birds of prey may be roughly divided into two classes, the hawks and the owls, the first feeding by day and the other by night. Of the eagles we need say but little. They are now so rarely found in the civilized districts that their influence for good or ill is practically nothing, except upon the game, and of that no doubt, they destroy a large quantity. HAWKS.Of the hawks there are eleven species, occurring regularly in this Province in greater or less abundance every season. [3] Hawk, Broad-winged Hawk, Rough-legged Hawk and Sparrow Hawk.Nearly everyone knows the Marsh Hawk and has seen it gracefully skimming over the low meadows, occasionally hanging poised over one spot for a second or two, and then dropping down into the long grass ; this drop generally means the death of a meadow mouse, sometimes, but more rarely, a Irog; of these two creatures its food principally consists, and the number of meadow mice destroyed by each of these birds in a season must be something enormous. As many as eight have been found in the stomach of one of these hawks, and four or five quite frequently. The hawk's digestion is very rapid, and their hunting and feeding is continued with but few intermissio...

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