Abstract
Calcium antagonists, e.g. verapamil, prevent exercise-induced asthma. This protective effect may proceed from inhibition of contraction of bronchial smooth muscle, release of mediators by primary effector cells, e.g. mast cells, or both. Therefore, we studied the inhibitory effect of increasing concentrations of verapamil on bothin vitro antigen-induced degranulation and ionophore A23187-induced release of labelled serotonin by rat peritoneal mast cells. There was a dose-dependent inhibition by verapamil of both ovalbumin-induced degranulation of mast cells passively sensitized by incubation with mice IgE-rich serum and ionophore-induced release of tritiated serotonin by mast cells previously incubated with (3H)-5HT; the 50% inhibiting concentration was 1·4×10−4 mol l−1 and 5·2×10−5 mol l−1, respectively. An attractive explanation of our results is that verapamil inhibits the antigen-induced release of mediators by mast cells through its calcium antagonist effect. Our results also suggest that the preventing effect of calcium antagonists on asthma may be multi-factorial since other authors have clearly shown that these drugs inhibit contraction of guinea-pig tracheal smooth musclein vitro.
Similar content being viewed by others
References
J.C. Foreman, M.B. Hallet andJ.L. Mongar,The relationship between histamine secretion and calcium uptake by mast cells, J. Physiol., Lond.271, 193–214 (1977).
M. Kohlhardt, B. Bauer, H. Krause andA. Fleckenstein,New selective inhibitors of the transmembrane Ca conductivity in mammalian myocardial fibres, Experientia28, 288–289 (1972).
A. Fleckenstein andK. Nakayama, Interaction of vasoactive ions and drugs with Ca dependent excitation-contraction coupling of vascular smooth muscle. InCalcium Transport in Contraction and Secretion, pp. 555–566 (EdsE. Carafoli et al.) North Holland Publishing Company 1975.
G. Sommers, G. Devis, E. Van Obberghem andW.J. Malaisse,Calcium antagonists and islets function, Endocrinology99, 114–124 (1976).
M.O. Lonchampt, N. Romquin, C. Bonne andF. Regnault,Inhibition of prostacyclin release from endothelial cells by verapamil, Vth Intern. Conf. Prostaglandins, Florence. Abst. 447 (1982).
P. Addonizio, C.A. Fisher andL.H. Edmunds,Effects of verapamil and nifedipine on platelet activation. Circulation 62, supp. III, Abst. 326 (1980).
H. Johnson,Effects by nifedipine on platelet function in vitro and in vivo, Thromb. Res.21, 523–528 (1981).
E. Middleton Jr.,Anti-asthamtic drug therapy and calcium ions: review of pathogenesis and role of calcium, J. Pharmaceut. Sci.69, 243–251 (1980).
J. Cerrina, A. Denjean, G. Alexandre, A. Lockhart andP. Duroux,Inhibition of exercise-induced asthma by a calcium antagonist, nifedipine, Am. Rev. resp. Dis.123, 156–160 (1981).
P.J. Barnes, N.M. Wilson andM.J. Brown,A calcium antagonist, nifedipine modifies exercise-induced asthma, Thorax36, 726–730 (1981).
K.R. Patel Calcium antagonists in exercise-induced asthma, Br. med. J.282, 932–933 (1981).
B.B. Lewine andN.M. Vaz,Effect of combinations of inbred strain, antigen and antigen dose on immune responsiveness and reagin production in the mouse. A potential mouse model for immune aspect of human atopic allergy, Int. Arch. Allergy39, 156–171, (1970).
A. Prouvost-Danon, J. Wyczolkowska, R. Binaghi andA. Abadie,Mouse and rat IgE. Cross sensitization of mast cells and antigenic relationships, Immunology29, 151–162 (1975).
Z. Ovary,Immediate reaction of the skin of experimental animals provoked by antigen-antibody interaction, Prog. Allergy5, 459–508 (Karger, Basel 1958).
C. Mazingue, J.P. Dessaint andA. Capron,3 H serotonin release: an improved method to measure mast cell degranulation, J. Immunol. Methods21, 65–77 (1978).
B. Uvnäs, Correlation between morphological and biochemical events on antigen-induced histamine release from rat mast cells. InMechanisms in Allergy, pp. 369–383 (EdsL. Goodfriends, A.H. Sehon andR.P. Orange), Marcel Dekker, New York 1973.
D.J. Triggle, Calcium antagonists: basic chemical and pharmacological aspects. InNew Perspective on Calcium Antagonists (EdG.B. Weiss), Clinical Physiology Series, American Physiological Society, Bethesda, Maryland 1981.
B.D. Gomperts, S. Cockroft, J.P. Bennet andC.M.S. Fewtrell,Early events in the activation of calcium dependent secretion: studies with rat peritoneal mast cells, J. Physiol., Paris76, 383–393 (1980).
T.J. Sullivan andL.J. Brown, Role of calcium in mediator release from mast cell. InNew Perspectives on Calcium Antagonists (Ed.G.B. Weiss), Clinical Physiology Series, American Physiological Society, Bethesda, Maryland 1981.
W.L. Parker andE. Martz,Calcium ionophore A23187 as a secretagogue for rat mast cells: does it bypass inhibition by calcium flux blockers? Agents and Actions12, 276–284 (1982).
B. Diamant andS.A. Patkar,Stimulation and inhibition of histamine release from isolated rat mast cells. Dual effects of the ionophore A23187 Int. Archs Allergy appl. Immun.49, 183–207 (1975).
E. Middleton Jr.,Effect of smooth muscle calcium antagonists on human basophil histamine release, Biochem. Pharmac.30, 2867–2869 (1981).
J. Cerrina, A. Renier, A. Floch, P. Duroux andC. Advenier,Effects of calcium antagonists on guinea-pig tracheal contraction induced by various agonists, Am. Rev. resp. Dis.125, Abst. 226 (1982).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Legrand, A., Cerrina, J., Bonne, C. et al. Inhibition of rat mast cell degranulation by verapamil. Agents and Actions 14, 153–156 (1984). https://doi.org/10.1007/BF01966635
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01966635