1. The response of the isolated jejunum of the sensitised guinea‐pig to the anaphylactic antigen resembles that produced by venoms and by S.R.S. in its latency, in the time required for relaxation, and in the after‐changes in excitability of the muscle. 2. The contractions of the jejunum of the guinea‐pig to antigen, to histamine, and to the slow‐reacting muscle‐stimulant substance (S.R.S.) formed by venoms were compared under various conditions of decreased reactivity of the muscle. These were brought about by administration of S.R.S., lysocithin, histaminase (Torantil), CO2, the toxin of Cl. welchii type A, and by photodynamic action. In most cases the responses to histamine, S.R.S., and antigen were depressed to the same extent. After repeated treatment with S.R.S. the response to S.R.S. was greatly reduced or abolished, that to histamine was unimpaired, and the response to the antigen was only slightly affected. During recovery from lysocithin poisoning the response to the antigen was only slightly reduced, while those to S.R.S. and histamine were greatly reduced. After treatment with the toxin of Cl. welchii type A the response to S.R.S. was greatly reduced, whereas those to histamine and to the antigen were unimpaired. A similar dissociation was observed with the guinea‐pig's uterus after lysocithin. 3. The inability of the jejunum of the guinea‐pig to respond to histamine when CO2 has been bubbled through the solution containing it does not result from the formation of a loose but inactive compound of histamine with CO2, but from an effect of CO2 on the muscle, causing a decrease in its reactivity to various stimuli. 4. The intra‐arterial injection of antigen into the isolated perfused lung of the guinea‐pig causes the liberation of a slow‐reacting musclestimulant substance into the outflowing perfusate. 5. Fresh saline extracts of sensitised lung show an increase in their S.R.S. content after incubation with antigen, but extracts of tissue desiccated after treatment with antigen and subsequently re‐extracted show no such increase. 6. Fresh and desiccated extracts of sensitised jejunum incubated with antigen behave like lung extracts, but fresh saline extracts of sensitised uterus and liver similarly treated show no increase in activity. 7. Desiccated as well as fresh extracts of intestine treated with cobra venom show a striking increase in their content of S.R.S. 8. It is concluded that the anaphylactic contraction of smooth muscles is in part due to the liberation of histamine and probably in part also to S.R.S., which is liberated and not formed in the antigenantibody reaction.
It is well known that salicylic compounds are of value in the treatment of reeopiized allergic conditions snch as rhenniatic fever and astlima. It has also been shown that salicylate will prevent precipitate formation when added to a mixture of egft nlhnmin and antihody iii vitro (Cobnrn and Kapp, 11)48). Jager and Nidjer.soii (1947) repoit sodium salicylate prevents antihody' formation to II and O antifjens in rhenmatie fever patients injected with typhoid vaeeines. Perry (1941) was not ahle to affect the development of ng'^lutinins following T.A.B. vaecinatinn in tlie pieseiu-e ol! aeetyl salicylie add administration. In an attempt to invcstis^ate this prohlem further we have investigated the effect of salieylates on the release of histamim-and slow-reacting suhstanee I Kellavvay and Trethewie, 1940) in anaphylaxis. METHODS. Lung perfitsion.Guinea-pigs were sen-sitized by the siibeutaneoua injection of 15 mg. erystnlline eggalbumin (kindly prepared hy Dr. Trautnor). Injcetions wero made in strriie saline (30 mg. albumin per ml.). The aiiiinala were .stunned hy :i light hlow o» thr head 6-9 werks after the Bensitizing injection and tho lungn perfiisiul as descrihed l.y Ki'll.-nvny and Tretliewie (1940). Tn certnin inHtancos sodinm salicyhitc or acetyl sitlicylic acid (lOn, .^O, 25, 12-n or (j-3 me. per 10(1 ml.) was diRsolved in the Tyi-ode used for porfusion of the hmfr. In these exporimenta antigen was dissolved in a similar solution immediately prior to injcotion. When the blood was washed out of the lungs the rate of perfusion was Bet at 1 ml. per minute, and after collection of the first sample (3 minutes) egg-albumin dissolved in Tyrode was injected from a. ayringc into the jjulnionaiy artery in a volnmc of 0-5 ml. after the flow was first interrupted. The flow was rc^estahUslied after l\ minutes. Porfusion samples were then collected for 10 minutes (80) and for another 5 minutes (S3). The volumes wei-e measured and all the samples l)oiled immediately and quickly cooled. assai/.Histamine WHS assayed as histamiue aoid-phosphato. The samples were assayed for histamiue and S.R.S. on the isolated jejunum of the guinea-pig (Trethewie and Kellawav, 1940). In some instances selective inhibition of the respo^nse of the gut to perfusion samples was 1 This work was carried ont with the aid of a grant from the National Health nnd Medical Research Council.
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