Histamine is released during anaphylactic shock and accounts for many of the observed symptoms. In recent years, interest has been focused on 5-hydroxytryptamine (5-HT) as another amine involved in the anaphylactic reaction. The present study was undertaken to assess the relative importance of histamine and 5-HT in anaphylactic shock in different species. The rat is particularly suitable for this work as its tissues can be preferentially depleted of either of these amines (Parratt & West, 1957 b) and severe shock can be consistently produced by using Haemophilus pertussis vaccine with the sensitizing dose of antigen (Sanyal & West, 1958). In this species the effect on the anaphylactic reaction of depletion of tissue histamine and 5-HT and of specific antagonists of these substances was therefore determined. In addition, the amine release from tissues was studied in the rat as well as in the guinea-pig, rabbit and dog.
METHODSFemale albino rats (100-150 g), adult guinea-pigs, adult rabbits and young dogs were used.Sensitization. Fresh egg white, which had been mixed with an equal volume of normal saline (aqueous NaCl 0-9 % (w/v)) and strained, or horse serum was used as antigen. Rats were sensitized by an intraperitoneal injection of either 1 ml. of egg white or a mixture of 1 ml. of horse serum and 1 ml. of H. pertussis vaccine, phase I, containing 20,000 x 106 organisms (Sanyal & West, 1958). Guinea-pigs were sensitized by an intraperitoneal injection of0-5 ml. of horse serum. Rabbits received 1 ml. of horse serum intraperitoneally on each of 6 consecutive days. Dogs were sensitized by a subcutaneous injection of 2 ml. of horse serum, followed 2 days later by an intravenous injection of 3 ml. of horse serum.Challenge. All animals were challenged by an intravenous dose of 1 ml. of antigen. This was given 12-18 days after the last sensitizing dose in rats, 21-28 days in guinea-pigs, 14-20 days in rabbits, and 20-30 days in dogs.Assessment of 8hock. The symptoms of shock in the rat were recorded as previously described (Sanyal & West, 1958). Development of asphyxia was taken to indicate the presence of anaphylactic shock in the guinea-pig. A marked fall in blood pressure indicated shock in the rabbitand dog.
R. K. SANYAL AND G. B. WESTDepletion of tissue amines in the rat. To deplete the skin of its histamine before challenge with the antigen, five doses of polymyxin B were given intraperitoneally over 3 days (Parratt & West, 1957b), commencing 9 days after sensitization. To deplete the skin and intestine of their 5-HT, one dose of reserpine (10 mg/kg) was given intraperitoneally 24 hr before the challenge. To deplete the stomach and jejunum of their histamine, a dose of 900 r total body irradiation (Eisen, Ellis & Wilson, 1956) was given 6 days after sensitization. To lower the skin histamine of several of the irradiated rats, repeated doses of polymyxin B were given during the 3 days before the challenge.Use of specific antagonists in the rat. Thirty minutes before the challenge, rats received intraperitoneal ...
