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.

WE have recently shown [1937a] that cobra venom causes the release of histamine from perfused lungs of cats and guinea-pigs. The experiments reported in the present paper concern the liberation of histamine from liver and lungs of other animals and the manner in which this effect may be produced.One of the actions of cobra venom is to cause haemolysis; this is not a direct effect of the venom on the red blood corpuscle but results from its action on lecithin. Kyes [1904] in Ehrlich's laboratory found that if cobra venom is brought into contact with lecithin a haemolytic substance is produced. Delezenne & Fourneau [1914] showed that this substance is a derivative of lecithin. The cobra venom contains a lecithinase which splits off oleic acid from lecithin. The resulting rest, lysocithin, is powerfully haemolytic. It appeared conceivable that the formation of lysocithin might account for effects of the venom, other than haemolysis and that its formation in the tissues might make the cells permeable to their histamine. Although this theory has not hitherto been put forward in this form, observations of Belfanti [1925, 1928], Guerrini [1925] and Houssay and his co-workers [Houssay, 1930] suggest that the formation of lysocithin may play a dominant role in the symptomatology of snake venom poisoning. They showed that the injection of lysocithin into animals caused symptoms resembling in some respects those caused by snake venoms. On the other hand, Belfanti's results on the action of snake venoms on emulsions made from different organs seemed to exclude the formation of lysocithin in all the tissues tested (heart, liver, kidney,

No abstract

No abstract

No abstract