5-hydroxytryptamine and Histamine as Mediators of T H E Vascular Injury Produced by Agents Which Damage Mast Cells in Rats* by Donald

No single agent has been found which accounts for the hyperemia and increased vascular permeability associated with many common reactions to injury. Histamine appears to be important in some reactions, but there is abundant evidence that it is not the sole active agent, and in many reactions may not be the major factor. The following experiments demonstrate that the edema produced in the rat by ovomucoid and three other agents which damage mast cells is mediated by the combination of 5-hydroxytryptamine and histamine, or closely related substances. In previous studies (1) of the acute vascular reaction produced by ovomucoid in rats it was shown that the edematous reaction in the skin was related to the distribution and concentration of mast cells in this tissue. Histamine was found to be associated with the mast cells and was shown to be released from tissues by ovomucoid. These parallelisms suggested that the histamine released might be a major factor in the production of hyperemia and edema in the rat. However, a direct correlation was not observed between the quantity of histamine released and the amount of edema produced. This finding suggested that another agent or agents present in skin might be involved in the production of edema. The occurrence of material with the biological and chemical characteristics of 5-hydroxytryptamine in rat skin and its association with mast cells (2) induced us to test synthetic 5-hydroxytryptamine for its capacity to produce increased vascular permeability and edema. When injected subcutaneously, 5-hydroxytryptamine was found to be an exceedingly potent agent in this respect. This raised the question of whether 5-hydroxytryptamine, operating alone or in combination with histamine, might not mediate the edema pro-