The distribution of substance P and 5‐hydroxytryptamine in the central nervous system of the dog

Amin, A. H.; Crawford, T. B. B.; Gaddum, J. H.

doi:10.1113/jphysiol.1954.sp005229

Cited by 680 publications

(195 citation statements)

References 34 publications

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“…The pharmacological analysis of extracts of the central nervous system led to the conclusion that 5-hydroxytryptamine (HT) was present in such extracts and was distributed in a way that suggested it might play a part in the physiology of certain nervous centres and particularly those near the 3rd and 4th ventricles (Twarog and Page, 1953;Amin, Crawford, and Gaddum, 1954). A study of the distribution of the enzyme 5-hydrotryptophan decarboxylase, which forms HT, strengthened this conclusion (Gaddum and Giarman, 1956).…”

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confidence: 73%

Some Central Actions of 5‐hydroxytryptamine and Various Antagonists

Gaddum

Vogt

1956

British Journal of Pharmacology and Chemotherapy

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confidence: 73%

Some Central Actions of 5‐hydroxytryptamine and Various Antagonists

Gaddum

Vogt

1956

British Journal of Pharmacology and Chemotherapy

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“…The site and mechanism of this action are not yet evident. It is known that 5-hydroxytryptamine is present in the nervous system (11), that it has a competitive action with acetylcholine on the molluscan heart (12), and that it initiates nerve reflexes (13). These actions suggest that 5-hydroxytryptamine may be another neurohumor.…”

Section: Discussionmentioning

confidence: 99%

5-Hydroxytryptamine and Histamine as Mediators of the Vascular Injury Produced by Agents Which Damage Mast Cells in Rats

Rowley

Benditt

1956

The Journal of Experimental Medicine

286

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No single agent has been found which accounts for the hyperemia and increased vascular permeability associated with many common reactions to injury. Histamine appears to be important in some reactions, but there is abundant evidence that it is not the sole active agent, and in many reactions may not be the major factor. The following experiments demonstrate that the edema produced in the rat by ovomucoid and three other agents which damage mast cells is mediated by the combination of 5-hydroxytryptamine and histamine, or closely related substances.In previous studies (1) of the acute vascular reaction produced by ovomucoid in rats it was shown that the edematous reaction in the skin was related to the distribution and concentration of mast cells in this tissue. Histamine was found to be associated with the mast cells and was shown to be released from tissues by ovomucoid. These parallelisms suggested that the histamine released might be a major factor in the production of hyperemia and edema in the rat. However, a direct correlation was not observed between the quantity of histamine released and the amount of edema produced. This finding suggested that another agent or agents present in skin might be involved in the production of edema.The occurrence of material with the biological and chemical characteristics of 5-hydroxytryptamine in rat skin and its association with mast cells (2) induced us to test synthetic 5-hydroxytryptamine for its capacity to produce increased vascular permeability and edema. When injected subcutaneously, 5-hydroxytryptamine was found to be an exceedingly potent agent in this respect. This raised the question of whether 5-hydroxytryptamine, operating alone or in combination with histamine, might not mediate the edema pro-

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“…The compounds listed in Table I (Bonnycastle and Bradley, 1956) and usually consisted of four doses given over two days, the animals being Amin, Crawford, and Gaddum (1954).…”

Section: Methodsmentioning

confidence: 99%

Anticonvulsant Compounds and 5‐hydroxy‐tryptamine in Rat Brain

Bonnycastle

Giarman

Paasonen

1957

British Journal of Pharmacology and Chemotherapy

105

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In rats, a series of anticonvulsant compounds have been shown to cause a significant elevation of brain 5-hydroxytryptamine (5-HT) levels in comparison with control values. This increase in 5-HIT only occurred in brain tissue and was not observed in spleen, upper small intestine or blood. Elevation of brain levels of 5-HT by iproniazid (Marsilid) or 5-hydroxytryptophan failed to give protection against the convulsant or lethal action of lept-zol (75 mg./kg.).The effect of phenytoin (diphenylhydantoin, Dilantin) in preventing the response of the pituitary-adrenal system to various standard procedures, known to cause a discharge of the adrenocorticotrophic hormone (ACTH) and a resultant fall in adrenal ascorbic acid, has been studied both for a direct action of the drug upon the adrenal gland itself and a possible alteration in some central mechanism (Bonnycastle andBradley, 1956, 1957). As it appeared fairly clear that, initially at least, the interference with the response is central in origin since the adrenal cortex remains normal in its responsiveness to exogenous trophic hormone, it was of interest to examine the levels of one or other of the suggested transmitting substances in the brain. In a preliminary report (Bonnycastle, Paasonen and Giarman, 1956) the 5-hydroxytryptamine (5-HT) content of the brains of rats treated with phenytoin was shown to be elevated approximately twofold over that of untreated control animals. The present paper deals with the brain levels of 5-HT in rats treated with other anti-epileptic drugs in use. Unlike phenytoin, none of these substances has any inhibitory effect upon the pituitary-adrenal system. METHODSMale rats of the Sprague-Dawley strain weighing 100 to 300 g. were used in these experiments. The compounds listed in Table I were examined. While the dosage varied considerably, an attempt was made to use doses which have been reported to be anticonvulsant in the rat against one or other convulsant procedure.Since many of the substances used are insoluble in any suitable media, some problems of uniform administration arose. After some preliminary experiments, the most satisfactory method was to weigh out the individual doses and suspend them as microcrystalline preparations for intraperitoneal injection. No attempts were made to determine the minimal effective dose or the duration of effect. The original dosage regimen was based on the previous study (Bonnycastle and Bradley, 1956) and usually consisted of four doses given over two days, the animals being

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The distribution of substance P and 5‐hydroxytryptamine in the central nervous system of the dog

Cited by 680 publications

References 34 publications

Some Central Actions of 5‐hydroxytryptamine and Various Antagonists

Some Central Actions of 5‐hydroxytryptamine and Various Antagonists

5-Hydroxytryptamine and Histamine as Mediators of the Vascular Injury Produced by Agents Which Damage Mast Cells in Rats

Anticonvulsant Compounds and 5‐hydroxy‐tryptamine in Rat Brain

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