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J R VANE

Publications and source records attributed to J R VANE.

At least 19 recordsLinked to original sources

A SENSITIVE METHOD FOR THE ASSAY OF CATECHOL AMINES.

A strip of fundus from a rat's stomach was suspended in Krebs solution containing 5-hydroxytryptamine. Movements of the muscle were recorded by means of a frontal writing lever giving a magnification of sixteen-times. The strip relaxed when isoprenaline, adrenaline or noradrenaline was added to the organ-bath in concentrations of 0.2 to 2 ng/ml. The preparation was most sensitive to isoprenaline and least sensitive to noradrenaline. The components of a mixture of two catechol amines could be assayed by superfusing the rat stomach and a chick rectum in the same stream of fluid.

Amines↗

A SENSITIVE METHOD FOR THE ASSAY OF ANGIOTENSIN.

A method is described for the assay of angiotensin on the rat colon. Under the conditions of the assay, the preparation is sensitive to angiotensin and relatively insensitive to 5-hydroxytryptamine, to histamine and to other substances which might be present in blood. Bradykinin and catechol amines do not interfere with the assay. Evidence is given for the specificity of the angiotensin receptors.

Amines↗

THE USE OF ISOLATED ORGANS FOR DETECTING ACTIVE SUBSTANCES IN THE CIRCULATING BLOOD.

A method is described for the assay of circulating hormones after their injection or release into the circulation. The method is applicable to cats, dogs and rabbits, and consists of bathing or superfusing isolated smooth muscle preparations in a stream of heparinized arterial blood taken from and returned to the animal at a constant rate. The tone of the smooth muscle preparations was affected by small changes in the concentrations of various amines. Thus increases in blood concentrations of catechol amines can be assayed with the rat stomach strip and chick rectum preparations. The proportions of adrenaline and noradrenaline in a mixture can be determined. Circulating histamine can be assayed on the blood-bathed guinea-pig ileum and bradykinin on the rat duodenum preparations. The uses and limitations of the technique are discussed.

Amines↗

An analysis of the direct and indirect actions of drugs on the isolated guinea-pig ileum.

The responses of the isolated guinea-pig ileum to coaxial stimulation of its nerves, to histamine, acetylcholine, bradykinin, nicotine, tetramethylammonium, 1,1-dimethyl-4-phenyl-piperazinium iodide and 5-hydroxytryptamine were studied, before and during anoxia, cooling, or exposure to hyoscine, phenoxybenzamine hydrochloride, morphine or hexamethonium. Dose ratios were used to determine the amount of block induced by these procedures. With the response to coaxial nerve stimulation as an indication of the excitability of the nervous tissue, it was found that anoxia or cooling abolished the response to single shocks. Under these conditions the response of the ileum to histamine, acetylcholine and bradykinin was hardly affected, indicating a direct action of these substances on the muscle fibres. The effects of nicotine, tetramethylammonium, dimethylphenylpiperazinium and 5-hydroxytryptamine were reduced to various degrees, and we have concluded that their main actions are indirect, through stimulation of cholinergic nerve fibres. When these indirect actions were prevented, increasing the dose revealed a direct action, a larger increase in dose being required for 5-hydroxytryptamine and dimethylphenylpiperazinium than for tetramethylammonium and nicotine. Exposure of the ileum to hyoscine and phenoxybenzamine showed that these direct actions of nicotine and tetramethylammonium were not only on acetylcholine receptors but also on receptors insensitive to hyoscine but sensitive to phenoxybenzamine. The main action of 5-hydroxytryptamine was on nervous elements, yet treatment of the ileum with phenoxybenzamine gave a higher dose ratio for 5-hydroxytryptamine than did treatment with morphine. The meaning of this result is discussed in relation to the general belief that receptors sensitive to morphine are in nervous tissue and receptors sensitive to phenoxybenzamine are in smooth muscle. We have concluded that morphine is only a partial antagonist of 5-hydroxytryptamine receptors in nervous tissue and that phenoxybenzamine antagonizes more 5-hydroxytryptamine receptors than those in smooth muscle.

Acetylcholine↗

The cardiac sphincter in the cat.

A study of the function of the lower end of the oesophagus in the cat confirms that it behaves as a true physiological sphincter, even though histological evidence for such a structure is absent. Sphincteric action is a function of the circular muscle fibres in the lowest 2 cm. of the oesophagus. Reflex changes in tone of the sphincter are mediated through the autonomic nervous system. The effects of possible neurohumoral transmitters, nerve stimulation, and antagonists have been studied.

Animals↗

The relative activities of some tryptamine analogues on the isolated rat stomach strip preparation.

The relative potencies of analogues of tryptamine and 5-hydroxytryptamine have been determined on the rat fundus preparation. This tissue had an amine oxidase activity, which, in the homogenate, was able to inactivate both tryptamine and 5-hydroxytryptamine to about the same degree. Amine oxidase inhibitors potentiated the action of tryptamine and many analogues on the isolated rat fundus preparation, but not the action of 5-hydroxytryptamine or of other hydroxytryptamines. This suggested that, in the isolated organ, the amine oxidase was unable to inactivate 5-hydroxytryptamine, but could inactivate tryptamine, 5-methoxytryptamine and many others. These results may be explained if it is supposed that tryptamine entered the cell, but because of the polar hydroxyl group 5-hydroxytryptamine did not. This hypothesis is supported by the oil/water partition coefficients. The structure/activity of the various tryptamine derivatives is discussed in the light of this assumption.

5-Methoxytryptamine↗

The distribution of methylpentynol and of methylpentynol carbamate in tissues and body fluids of cats.

A method is described for the estimation of methylpentynol and methylpentynol carbamate in body fluids and tissues. After intravenous administration, the distribution of these drugs throughout the body was found to be similar to that of ethanol. They entered cells, and crossed the blood-brain barrier and the placenta. They were excreted or secreted into the saliva, milk, gastric secretion, aqueous and vitreous humour, amniotic liquor, bile and urine. Methylpentynol was found in the expired air. Calculation of the volume of distribution and measurement of concentration in the tissues showed that both drugs were only slowly metabolized or excreted, suggesting the possibility that blood concentrations might rise cumulatively over a period of days.

Amnion↗

A sensitive method for the assay of 5-hydroxytryptamine.

The movements of a strip of fundus from a rat stomach, suspended in a 5 ml. bath at 37 degrees , 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 mug. 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.

Acetylcholine↗