110 The Chemistry of the Injured Cell 



HISTAMINE 



Histamine (Wolstenholme and O'Connor, 1956) is a di-amine 

 derived from the amino acid histidine. It is very widely distributed 

 in the tissues of all mammals. It is formed by the enzyme histidine 

 decarboxylase and destroyed by di-amine oxidase (histaminase). 

 Histamine dilates capillaries and increases their permeability to 

 protein and in some species dilates arterioles; it is thus an excellent 

 candidate for the role of mediator in inflammation. Lewis drew 

 attention to the similarity of the action of histamine and the vascu- 

 lar events of early inflammation and postulated the release by in- 

 jury of an histamine-like substance. 



Later studies showed that histamine was in fact liberated from 

 tissues damaged by a variety of means, particularly antigen-anti- 

 body reactions but including trauma, burns and infection. Hista- 

 mine was demonstrated in the circulation of the injured animals 

 and in the effluent from perfused tissues. It was also shown that a 

 large variety of organic bases could cause massive release of hista- 

 mine from tissues in the absence of apparent cellular damage 

 (Spector, 1958) . There is also evidence that injury may cause in- 

 creased activity of histidine decarboxylase and thus lead to in- 

 creased synthesis of histamine (Schayer, 1960) . The discovery of a 

 group of drugs that antagonised more or less specifically the effects 

 of histamine led to further advances. Treatment with these com- 

 pounds greatly reduced the inflammation caused by antigen-anti- 

 body reactions in certain situations, e.g. allergic rhinitis and 

 urticaria. However, the majority of inflammatory lesions both 

 natural and experimental were not affected by the anti-histamine 

 drugs. As a result it seemed that histamine had little or no part 

 in the inflammatory reaction in general. 



Some experiments conducted at University College Hospital 

 helped to resolve this discrepancy. When turpentine is injected 

 into the rat's pleural cavity, there is very rapid formation of an 

 inflammatory exudate. In the first thirty minutes, samples of this 

 exudate contain significant quantities of histamine but after this 

 time no histamine can be detected. This result suggests that hista- 



