THE MAST CELLS 



Histamine-liberation and disruption of mast cells play a comparatively small 

 part in the overall action of the liberator in the mouse, other toxic factors being 

 more prominent. In the rat, on the other hand, compound 48/80 appears to 

 exert a selective action on the mast cells. There are no other toxic side-effects, 

 oedema from the action of the locally released histamine and local irritation 

 of the skin being the prominent features. In the mouse, oedema and scratching 



IOO- 



80- 



60- 



40 



20- 



1 1 1 1 limn 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ''' '' 1 

 O 5 IO 15 20 25 30 35 



DAYS 



Fig. 42 



Long-term experiment. Effect of compound 48 80, continued over thirty-one days, 

 on the histamine content of subcutaneous connective tissue (dotted lines) and 

 ears (solid lines) of mouse and rat: histamine values expressed as per cent of 

 normal. Despite the repeated daily dosage not more than about half the avail- 

 able histamine can be liberated from the mouse. Full depletion in the rat is 

 followed by some recovery in the subcutaneous connective tissue but not in the ears. 



are never more than slight and may sometimes be absent. Biological assay 

 confirms that proportionately less histamine is released in the mouse despite 

 maximum tolerated doses of the liberator (amounting to 15 mg./kg.) being 

 administered. 



In the long-term experiments a state is reached in which most tissues of 

 the rat are completely devoid of both mast cells and histamine; further injections 

 now fail to elicit the clinical signs of histamine release. With continued dosage 

 some recovery of histamine and mast cells occurs in the subcutaneous connective 

 tissue of the rat but not in the ears. In the mouse under prolonged dosage of 

 compound 48/80, a steady state is reached when only about half of the histamine 



114 



