The mechanism of histamine release / W.D.M. Paton.

  • William Paton
Date:
[1956?]
Catalogue details

Licence: In copyright

Credit: The mechanism of histamine release / W.D.M. Paton. Source: Wellcome Collection.

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    within the general class of histamine releasers. Their pedigree starts with Anrep and his colleagues who showed in the course of studies on muscle that curarine was able to release histamine from it (Alam et al., 1939). It was later found by Macintosh and Paton (1949) that the ability to release histamine extended to a very wide range of organic bases. Indeed it seems that any compound possessing two or more basic groups carried on and separated by a sufficient aliphatic or aromatic scaffold is liable to have this property. The interest of these compounds however did not lie only in their number and their diversity of chemical structure, great as this was. They have a rather characteristic type of action exemplified in a simple way in the so-called “delayed depressor response”. Injected into a cat under chloralose, histamine causes a fall of blood pressure in 5-8 seconds (Fig. 1). But during this time the histamine liberators showed no action at all; and it is not until 20 or 80 seconds have elapsed, a period which Gray and Paton (1949) found later to correspond closely to one circulation time, that a depressor response occurs. When it comes however it is often as rapid as with histamine alone. Fig. 2 shows the delayed depressor response with a number of other compounds. The absence of action during the initial latent period is a nice demonstration that the drug itself has no direct effect on the blood vessels, and the absence of such a direct action can be shown in other ways, on isolated tissues or in one’s own skin. This can be shown too by the ineffectiveness of a liberator when all the mobilizable histamine has been released. The study of such depleted or refractory tissues is now almost a subject in itself (Feldberg and Talesnik, 1953). The release process appears to take place in a sharp burst, which has been termed “explosive” and is rather rapid. This follows from a comparison of the interval from the injection to the delayed depressor response with the circulation time; the release process must take only a few seconds or even less. A similar conclusion was reached by Feldberg and Paton (1951) in studies on perfused muscle, where it was
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