The liberation of histamine by certain organic bases / by F.C. MacIntosh and W.D.M. Paton.

  • William Paton
Date:
[1949?]
Catalogue details

Licence: In copyright

Credit: The liberation of histamine by certain organic bases / by F.C. MacIntosh and W.D.M. Paton. Source: Wellcome Collection.

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    formin produced effects on the blood pressure strikingly like those of histamine, and when the concentration of the depressor material was assayed in terms of histamine at various levels of dosage the same estimate was obtained. The depressor effect of such plasma was unchanged by previous administration of atropine in an amount sufficient to annul the effect of an equidepressor dose of acetylcholine, but it was abolished by an amount of Neoantergan just sufficient to abolish the effect of an equidepressor dose of histamine. Bovet and his co¬ workers (Bovet, Horclois & Walthert, 1944; Bovet, Horclois & Fournel, 1944) have shown that Neoantergan is a fairly specific antagonist to most of the effects of histamine, including its depressor action. Fig. 6 is the record of a typical experiment. In addition to its depressor activity, plasma withdrawn from a cat which had received licheniformin produced a contraction of the isolated guinea-pig’s ileum, indistinguishable from that produced by histamine. (Licheniformin itself in concentrations as high as 10-4 had no effect on the isolated gut, and did not modify its response to histamine.) It was usually possible to express the activity of the plasma in terms of the equivalent concentration of histamine, and the values then obtained agreed with those found in a parallel assay on the cat’s blood pressure, within the error of the two methods. In some experiments plasma obtained before the injection of licheniformin either produced a slow contraction of the gut muscle, or modified its sensitivity to histamine, so that the quantitative assay failed; but it was always clear that the injection of licheniformin had greatly increased the histamine-like activity of the plasma. The addition to the bath of atropine sulphate to give a concentration of 4 x 10~7, which abolished the effect of an equipotent dose of acetylcholine, slightly reduced the response to post-licheniformin plasma, and in about the same degree the response to histamine. Neoantergan (10~9) abolished the response to post-licheniformin plasma and to histamine, but not to other stimulants of smooth muscle (acetylcholine, K+, Ba++). The pre-treatment of the gut with excess of histamine (Barsoum & Gaddum, 1935) had a similar effect. Finally, extracts of plasma were made by Code’s (1937) modification of the method of Barsoum & Gaddum (1935), involving the destruction through acid hydrolysis of most of the substances acting like histamine on the blood pressure and on the isolated intestine which are likely to be present in tissue extracts. The extracts were assayed against histamine on these two test objects, atropine being present in each case. The results agreed with each other, and with those obtained for the fresh plasma. Fig. 7 and Table 1 give the result of such an experiment. Thus, soon after the administration of licheniformin to a cat its plasma is I found to contain a depressor substance which is not licheniformin itself, but which resembles histamine not only in its depressor effect, but also in its action on t
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