The 5-hydroxytryptamine-like actions of 5,6-dihydroxytryptamine.
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1. With isolated preparations of rat stomach fundus as well as of duodenum and ileum of rats and guinea-pigs, 5,6-dihydroxytryptamine and 5,6-diacetoxytryptamine caused a contraction which was antagonized by methysergide and lysergic acid diethylamide (LSD), but not by atropine. Pretreatment of the animals with reserpine did not decrease the effect of the two indoleamines on the isolated ileum and duodenum.2. In anaesthetized guinea-pigs, 5,6-dihydroxytryptamine and its diacetyl derivative caused bronchoconstriction which was antagonized by methysergide, but not modified by pretreating the animals with reserpine.3. In anaesthetized cats, 5,6-dihydroxytryptamine had, in general, a hypotensive effect which was reversed by hexamethonium.4. 5,6-Dihydroxytryptamine also caused aggregation of isolated rabbit and human platelets and inhibited the platelet aggregation induced by 5-hydroxytryptamine (5-HT) plus adrenaline.5. The pattern of action of 5,6-hydroxytryptamine and 5,6-diacetoxytryptamine was qualitatively the same as that of 5-HT, but the potency of the compounds decreased in the order 5-HT, 5,6-dihydroxytryptamine, 5,6-diacetoxytryptamine both in vitro and in vivo.6. It is concluded that 5,6-dihydroxytryptamine and its diacetyl derivative stimulate postsynaptic 5-HT receptors, but that their effect is weaker than that of 5-HT. (+info)
Interaction between tyramine and iproniazid on guinea-pig atria.
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The inhibition of monoamine oxidase (MAO) by iproniazid may be antagonized by large doses of tyramine as shown by the restoration, or otherwise, of inotropic responses to tyramine in isolated atria from guinea-pigs that had been treated with reserpine. (+info)
A pharmacological study of the adrenergic mechanisms involved in the stretch reflex of the decerebrate rat.
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1 The effects of catecholamine precursors, enzyme inhibitors, and monoamine depletors have been studied on the stretch reflex in the decerebrate rat.2L-DOPA alone had a biphasic effect, facilitation followed by inhibition and recovery of the reflex.3 About 10% of the preparations did not develop decerebrate rigidity. These preparations did not have a stretch reflex. Within 1 to 5 min of the injection of L-DOPA in these inactive preparations, a stretch reflex could be elicited.4 Control experiments indicate that L-DOPA was acting centrally after decarboxylation.5DL-dihydroxyphenylserine had an inhibitory effect, without a preceding facilitation.6 When L-DOPA was preceded by diethyldithiocarbamate (i.v.) or FLA-63 (i.p.), the predominant response was a sustained facilitation, without an accompanying inhibition.7 It is concluded that in the decerebrate rat, increased stretch reflex activity is associated with increased central levels of dopamine, and decreased stretch reflex activity with increased central levels of noradrenaline. The results are discussed with reference to the possibility that dopamine acts by liberating 5-hydroxytryptamine. (+info)
Restoration of the chronotropic effect of tyramine on rat atria after reserpine.
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1. The restoration by various sympathomimetic amines of the chronotropic response to tyramine was studied on the isolated atria of rats pretreated with reserpine. The atria were exposed to the "restorative" sympathomimetic amine for 10 min, washed over a period of 1 hr and then tested with 10 muM tyramine. The effect of noradrenaline, dopamine and norphenylephrine before and after inhibition of monoamine oxidase by 0.5 mM iproniazid were compared with their alpha-methyl and N-alkyl analogues in their ability to restore the chronotropic response to tyramine.2. Noradrenaline and adrenaline restored the chronotropic response to tyramine, the degree of restoration depending on the concentration of the restorative amine used. Noradrenaline after iproniazid and alpha-methylnoradrenaline were equipotent and were about 1,000 times more active than noradrenaline where monoamine oxidase was not inhibited. Dopamine, epinine, norphenylephrine, phenylephrine, octopamine, synephrine and isoprenaline in the absence of monoamine oxidase inhibition had no effect. Dopamine after iproniazid and alpha-methyldopamine were equipotent and were about 1/10 as active as alpha-methylnoradrenaline. Norphenylephrine after iproniazid and metaraminol were equipotent and were about 1/500 as active as alpha-methylnoradrenaline. Octopamine after iproniazid was even less active. The N-methylated analogues were about 1/10 as active as their nor-compounds but the N-isopropyl analogue, isoprenaline, was devoid of activity.3. Dopamine after iproniazid and alpha-methyldopamine were inactive if a dopamine-beta-hydroxylase inhibitor, disulphiram or sodium diethyldithiocarbamate, was present.4. It is concluded that, in atria of reserpinized rats, (a) protection from monoamine oxidase increases; (b) N-substitution decreases; and (c) hydroxyl groups at the beta-carbon and ring positions 3 and 4 increase the capabilities of a sympathomimetic amine to restore the chronotropic response to tyramine. (+info)
The possible role of histamine in the coritsone induced gastric acid hypersecretion of the guinea-pig.
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1. The effects of cortisone treatment combined with agents influencing histamine metabolism were studied on the free and total acid output in pylorus ligated guinea-pigs.2. It was found that reduction in the synthesis of histamine produced by the administration of alpha-methylDOPA significantly inhibited the acid response to cortisone.3. Enhancement of the oxidative deamination of histamine brought about by the administration of diamine oxidase or heparin inhibited cortisone induced acid hypersecretion significantly.4. Inhibition of the oxidative deamination of histamine by aminoguanidine and iproniazid resulted in a significant increase of the cortisone induced acid hypersecretory response.5. Inhibition of the methylation of histamine by chlorpromazine or 1,4-methylhistamine inhibited the cortisone induced hypersecretory response significantly.6. Studies with labelled histamine indicated that cortisone increases the sequestration of histamine to the stomach. (+info)
Radioautographic demonstration of 5-hydroxytryptamine- 3 H uptake by pulmonary endothelial cells.
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The lung is able to rapidly remove 5-hydroxytryptamme (5-HT) from the circulation by a Na(+)-dependent transport mechanism. In order to identify the sites of uptake, radioautographic studies were done on rat lungs which had been isolated and perfused with 5-HT-(3)H and 0 5 mM iproniazid, a monoamine oxidase inhibitor. In control experiments 10(-4)M imipramine was added to the perfusate to inhibit the membrane transport of 5-HT At the light microscope level, silver grains were seen concentrated near capillaries and in the endothelium of large vessels From electron microscope radioautographs a semiquantitative grain count was made and 90% of the silver grains were observed over capillary endothelial cells. The grains were found over the nucleus and cytoplasm of the cell and shewed no preferential association with any particular cytoplasmic inclusion bodies, organelles, or vesicles Other cell types were unlabeled except for a few mast cells, certain vascular smooth muscle cells, and one nerve ending. This radioautographic demonstration of the cell type responsible for the rapid removal of 5-HT from the lung circulation clearly establishes the existence of a new metabolic role for pulmonary endothelial cells. (+info)
Stimulation of the production of unesterified fatty acids in nerve endings of guinea-pig brain in vitro by noradrenaline and 5-hydroxytryptamine.
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1. Noradrenaline (1mm) and 5-hydroxytryptamine (1mm) stimulated the production of unesterified palmitate, oleate, stearate and arachidonate in nerve endings (synaptosomes) isolated from combined guinea-pig cerebral cortex and cerebellum. 2. Iproniazid phosphate (0.36mm) increased the concentrations of the same acids in osmotically ruptured synaptosomes. Further addition of 1mm-noradrenaline or 1mm-5-hydroxytryptamine reversed this increase. 3. Noradrenaline (0.01mm) stimulated the production of unesterified fatty acids in isolated synaptic membranes. 5-Hydroxytryptamine (0.01mm) stimulated the production of unesterified fatty acids in synaptic membranes and synaptic vesicles. (+info)
The role of monoamine oxidase in the response of the isolated central artery of the rabbit ear to tyramine.
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1. Monoamine oxidase activity was demonstrated histochemically throughout the media of the rabbit ear artery but not in the adventitia at its border with the media where the sympathetic nerve terminals are concentrated. Neither intensity nor distribution of enzyme activity was perceptibly altered up to 60 days after sympathetic denervation.2. Iproniazid and nialamide increased the sensitivity of the artery to intraluminal tyramine much more than that to extraluminal tyramine, so that the difference between the potencies for the two routes of administration became less marked.3. The results indicate that inactivation by monoamine oxidase in the media is a factor contributing to the relatively low potency of intraluminal tyramine on the artery. (+info)