Int. Archs Allergy appl. Immun. 52: 53-58 (1976)
Sequential Release of Histamine and 5-Hydroxytryptamine during Pinnal Anaphylaxis in the Mouse P. Miller and M. K. Church Department of Pharmacology, Roussel Laboratories Ltd., Swindon
Abstract. Histamine and 5-HT have been demonstrated to be involved in pinnal anaphylaxis in mice. Each predominates at different stages during the 30-min development of the reaction. The main mediator of the early stage of the reaction (0-10 min) is histamine, that of the middle stage (10-20 min) is 5-HT, and that of the final 20- to 30-min stage is, again, histamine. The source and mechanism of release of the 5-HT and the late histamine are, as yet, unknown but under investigation.
Received: January 17, 1976.
5-HT at different stages during the develop ment of the reaction and have demonstrated a sequential release of these amines.
Materials and Methods Animals Male CFLP mice, weighing 18-22 g, were ob tained from Anglia Laboratory Animals, Alconbury, Huntingdon. Reagents Horse serum (Horse serum No. 3) was pur chased from Wellcome Reagents Ltd., histamine diphosphate and compound 48/80 from Sigma Chemical Company, 5-hydroxytryptamine creatin ine sulphate from BDH Chemicals Ltd., mepyramine maleate from May and Baker Ltd., and methysergide bimaleate from Sandoz Ltd. Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 2:34:10 PM
The mouse produces two classes of ana phylactic antibodies, IgG, and IgE [8] which are capable of binding to mast cells. Combination of antigen with these immu noglobulins results in mast cell degranula tion and the local release of pharmacologi cally active substances [1]. The main me diators of anaphylaxis in the mouse have been shown to be histamine and 5-hydroxytryptamine (5-HT) [4, 9]. We have investigated the potential of the mouse pinna as a suitable site for the study of anaphylactic reactions [2] and in this paper report the identification of the main pharmacological mediators responsible for the increased vascular permeability ob served as a result of antigen-antibody inter action. Using specific antagonists, we have examined the parts played by histamine and
Miller/Church
54
Treatment
Mean are of blueing ± SEM, mm2
Inhi bition %
43.84 ±2.51
-
Saline
saline
Saline
mepyramine, 0.2 mg/kg 32.19±3.35*
Saline
mepyramine, 1.0 mg/kg 27.44 ±4.36** 37.4
Saline
mepyramine, 5.0 mg/kg 25.69 ±1.64** 41.4
26.6
Methysergide, 0.04 mg/kg saline
33.31 ±3.17
24.0
Methysergide, 0.20 mg/kg saline
21.44±3.66**
51.1
Methysergide, 1.00 mg/kg saline
15.21 ±2.70** 65.3
Methysergide, mepyramine, 1.00 mg/kg 5.0 mg/kg
1.12 ±0.32** 97.4
Compounds were administered subcutaneously 20 min before antigen challenge. Significance as compared with controls: * p
Sequential Release of Histamine and 5-Hydroxytryptamine during Pinnal Anaphylaxis in the Mouse P. Miller and M. K. Church Department of Pharmacology, Roussel Laboratories Ltd., Swindon
Abstract. Histamine and 5-HT have been demonstrated to be involved in pinnal anaphylaxis in mice. Each predominates at different stages during the 30-min development of the reaction. The main mediator of the early stage of the reaction (0-10 min) is histamine, that of the middle stage (10-20 min) is 5-HT, and that of the final 20- to 30-min stage is, again, histamine. The source and mechanism of release of the 5-HT and the late histamine are, as yet, unknown but under investigation.
Received: January 17, 1976.
5-HT at different stages during the develop ment of the reaction and have demonstrated a sequential release of these amines.
Materials and Methods Animals Male CFLP mice, weighing 18-22 g, were ob tained from Anglia Laboratory Animals, Alconbury, Huntingdon. Reagents Horse serum (Horse serum No. 3) was pur chased from Wellcome Reagents Ltd., histamine diphosphate and compound 48/80 from Sigma Chemical Company, 5-hydroxytryptamine creatin ine sulphate from BDH Chemicals Ltd., mepyramine maleate from May and Baker Ltd., and methysergide bimaleate from Sandoz Ltd. Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 2:34:10 PM
The mouse produces two classes of ana phylactic antibodies, IgG, and IgE [8] which are capable of binding to mast cells. Combination of antigen with these immu noglobulins results in mast cell degranula tion and the local release of pharmacologi cally active substances [1]. The main me diators of anaphylaxis in the mouse have been shown to be histamine and 5-hydroxytryptamine (5-HT) [4, 9]. We have investigated the potential of the mouse pinna as a suitable site for the study of anaphylactic reactions [2] and in this paper report the identification of the main pharmacological mediators responsible for the increased vascular permeability ob served as a result of antigen-antibody inter action. Using specific antagonists, we have examined the parts played by histamine and
Miller/Church
54
Treatment
Mean are of blueing ± SEM, mm2
Inhi bition %
43.84 ±2.51
-
Saline
saline
Saline
mepyramine, 0.2 mg/kg 32.19±3.35*
Saline
mepyramine, 1.0 mg/kg 27.44 ±4.36** 37.4
Saline
mepyramine, 5.0 mg/kg 25.69 ±1.64** 41.4
26.6
Methysergide, 0.04 mg/kg saline
33.31 ±3.17
24.0
Methysergide, 0.20 mg/kg saline
21.44±3.66**
51.1
Methysergide, 1.00 mg/kg saline
15.21 ±2.70** 65.3
Methysergide, mepyramine, 1.00 mg/kg 5.0 mg/kg
1.12 ±0.32** 97.4
Compounds were administered subcutaneously 20 min before antigen challenge. Significance as compared with controls: * p
