Release of Histamine and Formation of Smooth‐Muscle Stimulating Principles in Guinea‐Pig Lung Tissue Induced by Antigen and Bee Venom Phosphatidase A

Abstract

Release of histamine and formation of smooth‐muscle stimulating principles (spasmogenic lipids) occurred when minced guinea‐pig lung tissue was exposed to antigen or to bee venom phosphatidase A. In agreement with earlier reports the anaphylactic histamine release was a rapid process, and it could be inhibited by anoxia in the absence of glucose, and by potassium cyanide, ninhydrin and A’‐ethyl‐maleimide. The histamine release induced by phosphatidase A was not influenced by these inhibitors or by anoxia, and the release was slower than in anaphylaxis. The spasmogenic lipids formed had similar chromatographic and biological properties to those reported for the corresponding principles formed in anaphylaxis, and the process of formation was inhibited by oxygen lack and by the above enzyme inhibitors. One noteworthy feature of the spasmogenic lipid formation was that the inhibition caused by anoxia could not be counteracted by glucose. The results support earlier hypotheses regarding the mode of action of phosphatidase A on guinea‐pig lung tissue. It is suggested that mast cells are not necessarily involved in the formation of spasmogenic lipids occurring in connection with histamine release induced by phosphatidase A in the guinea‐pig lung. The bee venom fraction F II, which liberates histamine from rat tissues by a mechanism resembling that of compound 48/80, did not cause release of histamine or formation of spasmogenic lipids from the guinea‐pig lung tissue in concentrations up to 100 mug/ml.

Release of Histamine and Formation of Slow Reacting Substance in the Cat Paw Induced by Compound 48/80

“…This means either that the formation of SRS was not evoked during the histamine release processes induced by these agents or that some step in its formation was blocked. I t should be noted in this connection that in guinea-pig lung tissue the phosphatidase A induced formation of lipid-soluble smooth-muscle stimulating principles with biological properties similar to SRS is blocked by ninhydrin and N-ethylmalemide, whereas the release of histamine is not influenced (Fredholm and Strandberg 1969).…”

Ca++ Dependence of Histamine Release and Formation of Slow Reacting Substance in the Cat Paw

“…Both prostaglandin-like material and SRS were found, when guinea-pig lung (Fredholm and Strandberg 1969) and cat lung tissue (Ladinsky and Strandberg 1969) was incubated wih bee venom phospholipase A. The formation of these spasmogenic principles in guinea-pig lung was reduced by EDTA (Fredholm and Strandberg, unpublished).…”

Aspects of release of pharmacologically active substances from the lungs by chemical stimuli

“…It has moreover been known since the thirties that bee and snake venoms release histamine and other smooth muscle contracting substances from perfused guinea-pig lungs [11,33]. A venom fraction containing phospholipase A2 and free from histamine releasing basic polypeptides releases smooth muscle stimulating lipids from chopped lung tissue [34]. Despite this reservation, venoms or partially purified fractions are useful tools, when used with care.…”