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Biomedical subjects

J H GADDUM

Publications and source records attributed to J H GADDUM.

At least 19 recordsLinked to original sources

AN IMPROVED MICROBATH.

A method is described for the study of the actions of drugs and tissue extracts on small pieces of smooth muscle suspended in a bath with a capacity of 0.027 ml. The small size of the bath is an advantage when the total amount of active substance is small. The contractions are amplified 50- to 500-times and recorded isotonically, or approximately isometrically, with a pen writer. This apparatus has the advantage over earlier models that it is more compact and convenient and that the temperature of the muscle can be controlled. It has been used for the estimation of small quantities of acetylcholine and other substances in tissue extracts.

Acetylcholine↗

Assay of substance P on the fowl rectal caecum.

The optimum conditions for the assay of substance P on fowl rectal caecum have been studied. Effective concentrations vary from 0.01 to 0.5 u./ml.; it is remarkably insensitive to other polypeptides, such as bradykinin. The test can be made more specific by using a bath fluid containing antagonists for known interfering substances. A suitable antagonist for acetylcholine is atropine or hyoscine, for 5-hydroxytryptamine, methysergide and for catecholamines, ephedrine. The effects of histamine and adenosine compounds can be abolished by specific tachyphylaxis, in which the bath fluid contains an excess of the active substance itself. The assay is reasonably accurate. Woolf's index of precision (L) was estimated as 15.5 with a range (9) of 9.2 to 29.4. Simplified methods of calculating L, and the fiducial range, are described.

Acetylcholine↗

Assay of substance P on goldfish intestine in a microbath.

A technique is described for testing the effects of drugs on the intestine of goldfish in a microbath (0.05 ml.). This preparation may be used for the assay of substance P, which causes contractions of the muscle in doses as small as 1 m-u. Other substances in tissue extracts also act on this muscle, but the effects of most of these can be abolished by antagonists. Some tissues, however, contain an unknown substance which causes powerful contractions of the muscle and interferes with the assay of substance P. An attempt to demonstrate the release of substance P in the central nervous system was unsuccessful.

Animals↗

A comparison of the kallikrein-kinin system in sheep and dogs.

Three preparations of kallikrein, made from the urine of man, dog and sheep, all formed active kinins when incubated with the plasma of sheep or dogs. The six kinins could not be distinguished from one another by parallel assays on guinea-pig ileum, rat uterus and rat duodenum; they are thought to be identical, or nearly so. As judged by the amount of kinin produced, a sample of dog plasma appeared to contain about 4.3 times as much substrate as a sample of sheep plasma. This ratio did not depend on the kallikrein used. Attempts to compare the three kallikreins gave inconsistent results which may be due to presence in the preparations of kallikrein of other enzymes acting on the same substrate. Sheep plasma does not form kinins on contact with glass.

Animals↗

The extraction of human urinary kinin (substance Z) and its relation to the plasma kinins.

Human urinary kinin (substance Z) has been extracted by modifications of the methods previously described by Gomes (1955) and Jensen (1958). The separation of two oxytocic fractions from such extracts by paper pulp chromatography (Walaszek, 1957; Jensen, 1958) could not be confirmed. Substance Z could not be distinguished from kallidin, bradykinin or glass-activated kinin by parallel quantitative assays, thus confirming that these four substances are very closely related.

Biological Assay↗

A microbath.

A microbath, with a volume of less than 50 cubic millimetres, for testing the effects of drugs on small pieces of smooth muscle, is described. Drugs are applied automatically in any desired order and the record of their effects is amplified electrically. In this apparatus the response of small pieces of rat uterus to drugs is apt to be nearly all-or-none. Contractions of the muscle from a single ring of guinea-pig trachea were recorded. A fall of pH was found to reduce the effect of 5-hydroxytryptamine on this muscle while leaving the effects of tryptamine and acetylcholine unchanged.

Acetylcholine↗

Two kinds of tryptamine receptor.

There are two kinds of tryptamine receptor in the guinea-pig ileum, namely the M receptors which can be blocked with morphine and the D receptors which can be blocked with dibenzyline. Atropine, an atropine-like drug, cocaine, and methadone inhibit effects due to the M receptors, even after dibenzyline, but have no additional effect after morphine. Lysergic acid diethylamide, dihydroergotamine and 5-benzyloxygramine inhibit effects due to the D receptors, even after morphine, but have no additional effect after dibenzyline. The M receptors are probably in the nervous tissue and the D receptors are probably in the muscles.

Alkaloids↗