The release of physiologically active substances in animal tissues during anaphylaxis has been a subject of considerable interest for many years. Most of this interest has centered on the release of histamine from a bound to a free form, the latter being capable of producing marked physiological changes (1). However, despite the toxicity which can be attributed to histamine, attempts to explain all the alterations seen in anaphylaxis on the basis of histamine release alone have been unsatisfactory (2).Many of the effects produced by serotonin (5-hydroxytryptamine) in animals (3) resemble the manifestations of hypersensitivity reactions. In addition, patients with malignant carcinoid, a syndrome (4) in which there is present an excessive amount of serotonin, frequently show symptoms resembling those of an allergic process.. These findings have suggested that this amine may play a role in anaphylaxis and other allergic phenomena.Serotonin is found in the blood platelets of animals and man (5). Anaphylaxis is known to produce profound changes in these blood cells (6). Recently, Humphrey and Jaques (7) showed that both serotonin and histamine were released from platelets upon addition of purified antigen and antibody to normal rabbit platelets suspended in plasma. Also, Herxheimer (8) reported that in guinea pigs an interrelationship exists between desensitization and tolerance to serotonin.The present study was designed to determine whether serotonin is released during anaphylaxis. The experiments outlined below for serotonin are similar to those that were previously used to demonstrate the changes in blood histamine which occur during anaphylactic shock (9-12). Simultaneous determinations for both serotonin and histamine were carried out for comparative purposes. In this work, it has been shown that both amines appear in a free form in the plasma when a specific antigen is injected into sensitized rabbits.
MATERIALS AND METHODSThe rabbit was chosen for these experiments for several reasons: (a) the large amounts of both serotonin and histamine carried in the blood platelets, (b) the ease of obtaining serial blood samples, and (c) the ability of the rabbit to produce adequate amounts of antibody.Male rabbits (1.5 Kg.) were sensitized to either egg albumin or horse serum. Those sensitized to egg albumin were given 10 ml. of a 10 per cent solution in saline intraperitoneally every other day for four injections. Those sensitized to horse serum were given 1 ml. of the undiluted serum intraperitoneally every day for six days. Ater three to five weeks, the rabbits were used as indicated. At this time, complement fixation antibody titers were high.Siliconized glassware was employed wherever whole blood had to be handled. Blood for the in ritro studies was obtained by intracardiac puncture. Blood samples for the in vivo studies were obtained by means of a plastic tube inserted into the carotid artery.Both serotonin and histamine were determined in all samples of plasma and whole blood. For plasma, 2 ml. were treated accord...