112 The Chemistry of the Injured Cell 



there is some evidence that release of histamine from these cells 

 depends upon activation of this protease (Glennor and Cohen, 

 1960). 



5-HYDROXYTRYPTAMINE (5-H.T., SEROTONIN) 



This substance is a monoamine derived from the amino acid 

 tryptophane. Like histamine, it is widely distributed in animal 

 tissues and is thought to play a role as a neurohormone in the 

 brain. Like other monoamines it was thought to be a vasoconstric- 

 tor, but Rowley and Benditt (1956) showed that in very low con- 

 centrations in the rat it increased capillary permeability, i.e., had 

 a histamine-like action. In most other species, however, 5-H.T. 

 does not increase capillary permeability, so that any role it plays 

 as a mediator of inflammatory changes must presumably be con- 

 fined to the rat and perhaps the mouse. Compounds exist more or 

 less specifically antagonistic to 5-H.T. Dosage with such substances 

 considerably reduces the increased capillary permeability caused 

 in the rat by injection of certain large molecular substances, e.g. 

 egg white or dextran, suggesting that release of 5-H.T. is in part 

 the cause of this particular type of vascular reaction. It is known 

 also that in the rat, histamine liberators such as compound 48/80 

 release 5-H.T. too. However, administration of 5-H.T. inhibitors 

 to rats subjected to injury caused by turpentine, heat and x-rays 

 has failed to influence the course of inflammation. Thus no evi- 

 dence yet exists that 5-H.T. is important in true inflammation even 

 in the rat. In spite of these findings, there is ample evidence for the 

 release of 5-H.T. by a variety of injuries in a number of species, 

 an observation whose significance is yet to be revealed (Spector, 

 1958) . The substance might be liberated as a result of damage to 

 platelets (which occurs in the early stages of tissue injury) , or 

 lysis of mast cells, and perhaps play a role in the causation of pain 

 if not capillary permeability (see below) . 



PEPTIDES 



Peptides consist of varying numbers of amino acids joined by 

 peptide linkages and forming molecules too small to be considered 

 as proteins. Their possible role in inflammation has been suspected 



