408 IMMUNO-CATALYSIS 



Histamine has been reported to exercise three main pharmaco- 

 logical actions: 1 . An intense capillary dilator effect on the circula- 

 tory system. 2. An excitation of involuntary muscles of smooth 

 type of most organs. 3. A stimulation of secretory systems- 

 salivary, gastric, pancreatic, intestinal and lacrimal. 

 A prominent pharmacological action of histamine is its spasmogenic 

 action on smooth muscle of the bronchioles, gastro-intestinal tract, 

 uterus, ureters and gall bladder. Histamine indirectly induces arteri- 

 olar constriction or dilatation depending on the animal species or the 

 locality of the vascular bed in a given species. It causes dilatation of the 

 capillaries and venules, and thus causes hyperemia and skin wheals in 

 humans. The production of increased capillary dilatation and greater 

 capillary permeability is attributed to the action of histamine. However, 

 these effects also result from anoxia. The latter effect is involved in 

 the production of localized edema. Histamine is a potent stimulator 

 of the lymphatic flow. 



In guinea pigs, an intravenous injection of 0.3 to 0.5 mg. of histamine 

 per kg. guinea pig causes death by inducing spasm of the bronchial 

 muscle and suffocation. In rabbits, the administration of histamine 

 causes transient hypertension and then hypotension. The death of the 

 animal is due to circulatory failure which is secondary to a marked con- 

 striction of pulmonary blood vessels. In cats, dogs, and man, the blood 

 pressure falls rapidly upon the administration of histamine. Dogs are 

 killed by 1 to 3 mg. of histamine per kg. Man also is sensitive to 

 milligram quantities of histamine. The mouse, rat, and frog, on the 

 other hand, are very resistant to histamine, and the toxicity of histamine 

 is manifest only after receiving doses of 500 mg. or more. 



b. Distribution of Histamine. Histamine has been isolated from 

 intestinal mucosa (Barger and Dale, 1911), and detected in a variety 

 of tissues (Abel and Kubota, 1919). It has been isolated in crystalline 

 form from animal tissues (Best, et ah, 1927) and whole rabbit blood 

 (Code and Ing, 1937). Considering blood as the source of histamine, 

 the largest amount has been found in the rabbit and smallest in the cat. 

 In the mouse over 60 per cent of the histamine is found in the skin. 

 The tissues of the central nervous system are virtually devoid of hista- 

 mine, but histamine is found in large amounts in the peripheral sensory 

 nerves which are the only nerves capable of antidromic stimulation. 

 Seventy to 90 per cent of the blood histamine is held in an inactive 



