THE MAST CELLS 



Mast cells. In brief, the mast-cell picture of the injected ears twenty-four 

 hours after operation closely resembles that seen on day three of the 'subacute 

 dosage 1 experiment, there being widespread disruption of the mast cells. In 

 contrast, the ears on the opposite side which had not been directly injected 

 appear normal. However, it should be mentioned that in one animal there 

 were also signs of damage to mast cells in the mesenteric windows. 



Histamine. There was a significant difference in the histamine content of 

 the ears on the two sides twenty-four hours after injection, the injected ears 

 containing only an average of 6 ng./g. histamine as against 27 [xg./g. for the 

 opposite ears of the same animals. The latter figure is somewhat low, an average 

 value for the ears of an untreated rat being 44 u.g./g. Presumably some of the 

 injected 48 80 had reached the general circulation. 



Discussion 



The main fact emerging from these experiments on rats treated in various 

 ways with the powerful histamine-liberator, compound 48 80, is the parallelism 

 which exists between the histamine value of a particular tissue and its mast-cell 

 content. Thus, in the present work, the transitory fall of histamine in the 

 'acute dosage' experiment, the more prolonged fall in the 'subacute dosage' 

 experiment, and the sustained reduction in tissue histamine in the 'chronic 

 dosage' experiment, are all reflected in the changes in the mast-cell population 

 of the four tissues studied. 



Specificity and low toxicity of compound 48 80 



Intense shock follows the initial injection of compound 48 80 into the 

 peritoneal cavity of the rat. Soon, however, the animal acquires tolerance to 

 further daily doses which would once have been fatal. This gradual acquisition 

 of tolerance corresponds to the progressive loss of tissue histamine; and having 

 acquired tolerance the rats display no further signs of toxicity for at least thirty 

 days, the period of the 'chronic dosage' experiment. 



Thus we see that compound 48/80 produces shock in the rat only when there 

 is histamine to be liberated and that once the tissues are free of histamine, 

 compound 48/80 is no longer toxic. Its action in the rat, then, is that of a 

 specific histamine-liberator. 



Site of action of compound 48 80 



It is probable that histamine can be released in various ways, and it is 

 thought by some that the most common mechanism is through the activation 

 of a proteolytic enzyme in the blood (Rocha e Silva, 1953). However, the 

 ability of compound 48/80 to release histamine in the rat would appear to 



106 



