Removal of 5-hydroxytryptamine in the pulmonary circulation of rat isolated lungs.
TL;DR: It is concluded that the removal of 5‐HT by rat lungs involves a process of uptake and metabolism rather than one of absorption and storage, but this process is not the catecholamine Uptake2.
Abstract: 1
. Rat isolated lungs perfused via the pulmonary artery with Krebs solution removed 92% of the 5-hydroxytryptamine (5-HT) infused through it. This degree of removal was independent of concentration in the range from 5 to 100 g/ml.
2
. The removal of 5-HT by the lungs was inhibited by amitriptyline and desmethylimipramine (10−6–10−5m).
3
. The monoamine oxidase inhibitors, mebanazine and iproniazid (10−6–10−5m), inhibited the initial removal slightly, but their main effect was to preserve the 5-HT taken up and this 5-HT slowly reappeared in the effluent from the lungs. Tranylcypromine (5 × 10−7–10−6m) showed a combination of amitriptyline-like and mebanazine-like effects on the 5-HT removal in rat lung.
4
. Experiments with 3H-5-HT showed that although under normal conditions only 10% of the radioactivity appeared in the lung effluent as 5-HT within the first 5 min, the rest of radioactivity administered could be recovered in the effluent over 50 min as a metabolite, probably 5-hydroxyindoleacetic acid.
5
. The following amines were without effect on the removal of 5-HT by rat lungs: noradrenaline (6 × 10−7m), normetanephrine (5 × 10−6m), metaraminol (10−6m), reserpine (10−6–10−5m) and phenoxybenzamine (10−5m).
6
. We conclude that the removal of 5-HT by rat lungs involves a process of uptake and metabolism rather than one of uptake and storage, but this process is not the catecholamine Uptake2. The cells involved in this process might be either capillary endothelial cells or septal cells.
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TL;DR: It is suggested that agents which liberate prostaglandin endoperoxides and thromboxane A2 from perfused lungs do so by activating phospholipase A2.
Abstract: 1 A simple double-isotope assay for phospholipase A2 activity of perfused organs is described; Guinea-pig lungs perfused through the pulmonary circulation exhibit a low background enzyme activity. This activity is blocked by dexamethasone, betamethasone and hydrocortisone, mepacrine, procaine or chlorpromazine. Aspirin and indomethacin are without effect. 3 Mechanical trauma, antigen challenge or injections of bradykinin, rabbit aorta contracting substance-releasing factor (RCS-RF) or histamine increase "basal" phospholipase activity. The effect of these agents, except that of bradykinin, is blocked by dexamethasone or mepacrine. 4 The blocking effect of steroids is cumulative and dose-dependent. They do not work in cell-free systems. Inhibition by mepacrine is rapid and is effective in cell-free lung homogenates. 5 It is suggested that agents which liberate prostaglandin endoperoxides and thromboxane A2 from perfused lungs do so by activating phospholipase A2.
317 citations
TL;DR: In 1967, knowing that cheese is a common dietary trigger to migraine, Hanington fed tyramine, which it is known to contain, to affected subjects and by this action was able to initiate headache episodes.
Abstract: FOR some two hundred years, certain foodstuffs have been known to trigger migraine attacks1. In 1967, knowing that cheese is a common dietary trigger to migraine, Hanington2 fed tyramine, which it is known to contain, to affected subjects and by this action was able to initiate headache episodes.
234 citations
TL;DR: The results reported here suggest that a glucocorticoid receptor and the induction of gene expression are involved in the anti-inflammatory action of dexamethasone.
Abstract: GLUCOCORTICOIDS are potent anti-inflammatory agents, but the molecular mechanisms involved in this activity are not yet understood. The biological actions of various steroid hormones have been shown to be mediated by functional proteins synthesised following translocation of a hormone-cytoplasmic receptor complex into the nucleus1,2. It is still not clear, however, whether the anti-inflammatory effects of glucocorticoids are mediate via binding to a cytoplasmic receptor in target cells and subsequent activation of gene expression3, although glucocorticoid receptors have been demonstrated in HTC cells, liver5, thymocytes6 and lymphocytes7. The results reported here suggest that a glucocorticoid receptor and the induction of gene expression are involved in the anti-inflammatory action of dexamethasone.
203 citations
TL;DR: The contribution made by abnormal prostaglandin mechanisms to hypertensive disease should now take into account that a deficiency of prostacyclin and not PGE2 could be a major factor causing the elevated tension developed in vascular smooth muscle and the augmented vessel responsiveness to stimuli associated with hypertension.
179 citations
TL;DR: The primitive lung was little more than an air sac containing minute vessels in its walls for gas exchange that served as an accessory organ of breathing that allowed fishes seeking refuge from oxyg...
Abstract: THE primitive lung was little more than an air sac containing minute vessels in its walls for gas exchange. It served as an accessory organ of breathing that allowed fishes seeking refuge from oxyg...
131 citations
References
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TL;DR: Some of Gaddum's first publications were on the development of specific and sensitive methods for biological assay, and he maintained a deep interest in this subject for the rest of his life.
Abstract: Some of Gaddum's first publications were on the development of specific and sensitive methods for biological assay, and he maintained a deep interest in this subject for the rest of his life (see Feldberg, 1967). One of the methods which he developed was that of superfusion, first described by Finkleman (1930). In this technique the bathing fluid runs over the external surface of the tissue, and Gaddum (1953) called it \" superfusion \" by analogy with \"perfusion,\" in which the fluid runs through the tissue.
610 citations
556 citations
TL;DR: The movements of a strip of fundus from a rat stomach, suspended in a 5 ml.
Abstract: The movements of a strip of fundus from a rat stomach, suspended in a 5 ml. bath at 37°, are recorded by a spring-loaded lever. The muscle is stretched for 15 to 30 sec. between contractions. 1 ng. 5-Hydroxytryptamine (5-HT), 10 ng. acetylcholine or 2 to 10 μg. of histamine all produce contractions, giving tracings about 4 cm. high. In the presence of hyoscine (10−7) low concentrations of 5-HT can be assayed directly from mixtures of the three substances. Sympathomimetic amines interfere with the assay, but this can be overcome. The preparation is robust, potentially suitable for use with an automatic assay apparatus and 10 to 100 times more sensitive than the rat uterus.
529 citations
TL;DR: In this article, the counting of carbon-14 and tritium in blood, heart, kidney, liver, spleen, lung, and muscle tissue was investigated and the effect of dilution of such solvent and color quenched solutions was shown.
Abstract: Liquid scintillation counting of carbon-14 and tritium in blood, heart, kidney, liver, spleen, lung, and muscle tissue was investigated. The dissolution of tissues into two different solvent systems and their counting are discussed. The effect of dilution of such solvent and color quenched solutions is shown. Some counting efficiencies obtained for carbon-14, tritium, and suIfur-35 in different tissues and their variation are presented along with a general procedure for counting tissue samples. The liquid scintillation counting of whole tissues, although not possessing the efficiency of combustion techniques, is particularly useful for the assay of large numbers of samples. (auth)
302 citations
TL;DR: Measurement of the initial rates of noradrenaline uptake during perfusion with various concentrations of nonradioactive (+)- and (-)-noradrenalin showed that the uptake process exhibited stereochemical specificity, which suggested that diffusion did not play any significant role in the entry of nor adrenaline into the tissue.
Abstract: The uptake of noradrenaline by the isolated perfused rat heart was studied after perfusion with a medium containing various concentrations of (+/-)-[(3)H]-noradrenaline. Simultaneous measurement of the uptake of [(3)H]-noradrenaline and of the net increase in the noradrenaline content of the heart showed that [(3)H]-noradrenaline entering the heart both increased the tissue content and exchanged with endogenous noradrenaline. A large part (about 75%) of the endogenous noradrenaline pool, however, exchanged very slowly if at all with exogenous noradrenaline. The initial rates of noradrenaline uptake satisfied Michaelis-Menten kinetics with a Km for (+/-)-noradrenaline of 6.64x10(-7) M. Further analysis of the uptake process indicated that noradrenaline entered into at least two intracellular pools at different rates. Measurement of the initial rates of noradrenaline uptake during perfusion with various concentrations of nonradioactive (+)- and (-)-noradrenaline showed that the uptake process exhibited stereochemical specificity. The Km values for (+)- and (-)-noradrenaline were 13.9x10(-7) and 2.66x10(-7) M respectively. Cocaine acted as a potent competitive inhibitor of noradrenaline uptake. This finding suggested that diffusion did not play any significant role in the entry of noradrenaline into the tissue.
267 citations