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

  • Paton, William D. M.
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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    [Reprinted from the Journal of Physiology, 1949, Vol. 109, Nos. 1 and 2, p. 190.] PRINTED IN GREAT BRITAIN J. Physiol. (1949) 109, 190-219 612.015.34:547.415.1:547.781.5 THE LIBERATION OF HISTAMINE BY CERTAIN ORGANIC BASES By F. C. MACINTOSH and W. D. M. PATON From the National Institute for Medical Research, Hampstead, London (.Received 10 January 1949) Histamine is liberated from mammalian tissues by a variety of agents, most of which are of a complex nature chemically. They include antigens (in sensitized animals), peptone, trypsin, lysolecithin, animal venoms and certain bacterial toxins (for references see Feldberg, 1941). In addition, several basic drugs of relatively simple structure have been reported to liberate histamine. The release of histamine from skeletal muscle by curare alkaloids (Alam, Anrep, Barsoum, Talaat & Wieninger, 1939; Schild & Gregory, 1947) and by strychnine (Schild & Gregory, 1947) is well established; and that adrenaline has a similar action has been reported by Eichler & Barfuss (1940) and by Staub (1946). In the course of some pharmacological tests on licheniformin, an antibiotic base extracted from Bacillus licheniformis by Callow, Glover, Hart & Hills (1947), we found that the characteristic lowering of the cat’s blood pressure produced by the substance was due to the liberation of histamine. Further investigation showed that many other organic bases produced a depressor effect of the same kind, and for the same reason. A preliminary report of the results has already been made (Macintosh & Paton, 1947). METHODS Most of our experiments were carried out on cats or dogs. Cats were usually anaesthetized with chloralose; a few were anaesthetized with ether, or were decerebrated under ether. Dogs were anaesthetized with sodium barbitone, sodium phenobarbitone or a chloralose-urethane (1:10) mixture. Blood pressure was recorded in the usual way from a carotid artery, the anticoagulant fluid being either saturated Na2S04 solution, or more usually 0-9 % NaCl containing heparin. Blood samples for pharmacological tests were taken only in experiments in which no blood-pressure record was made; they were withdrawn from a carotid artery through a steel cannula filled with 1 % sodium heparin solution, into a syringe containing 0-05 c.c. of the same solution for each c.c. of blood. Plasma for pharmacological tests was obtained by centrifuging such blood samples without delay. We found that normal plasma so collected had no depressor activity when reinjected. Plasma samples and extracts were tested on the isolated ileum of the guinea-pig, suspended in Locke’s solution containing 0-004% MgCl2; the volume of the bath was 20 c.c. For some tests, atropine sulphate (4 x 10~7) or Neoantergan maleate (‘Anthisan’, May & Baker: 10~9) was added to the fluid in the bath. Other procedures are described in the text. Doses and concentrations of histamine are stated in terms of the base.