5-Hydroxytryptamine and Histamine as Mediators of the Vascular Injury Produced by Agents Which Damage Mast Cells in Rats

Abstract

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-

Pharmacological characterization of polycation‐induced rat hind‐paw oedema

“…This is to be expected since irritant agents cause release of these mediators (Spector & Willoughby, 1968) and poly-DL-lysine (Padawer, 1970;Ennis et al, 1980) and the polycation 48/80 (Kazimierczak & Diamant, 1978) degranulate mast cells. The lack of effect of mepyramine is not surprising, since histamine is not an important mediator of vascular permeability in rats (Rowley & Benditt, 1956;Wilhelm, 1962).…”

Tissue Mast Cells and Acute Inflammation in Experimental Cutaneous Mucormycosis of Normal, 48/80-Treated, and Diabetic Rats

“…The granule discharge appears to be the morphologic manifestation of the release of histamine and 5-hydroxytryptamine which have been shown to initiate hyperemia and increased vascular permeability (1,4). These processes precede or coincide with granulocytic margination and exudation; in short, the acute inflammatory response.…”

“…In the rat these substances have been identified as histamine, heparin, and serotonin (5-hydroxytryptamine) (4,5). It has also been shown that the tissue content of histamine closely parallels the number and granularity of the tissue mast cells and that histamine, heparin, and serotonin are released into the tissues when the tissue mast cells are depleted of their granules by various experimental means (1,4).…”

“…The tissue mast cells in the rat have been shown to play a part in the development of hyperemia, vascular permeability, edema formation, and wound healing (1)(2)(3). It appears that these processes, which are essential components of the normal inflammatory and reparative reaction, are elicited by the release of substances located in or on the cytoplasmic granules of the tissue mast cells.…”

Rats Resistant to the Dextran Anaphylactoid Reaction

“…The term "anaphylactoid reaction" was used by Selye in 1937 to describe the hyperaemia, pruritus and oedema of the extremities produced by the primary intraperitoneal injection of fresh egg-white into rats. Many years later, a similar reaction was shown to be produced by dextran, a carbohydrate polymer (Voorhees, Baker & Pulaski, 1951;.…”