Abstract
Exocytosis dependent on calcium and metabolic energy has been established as the mechanism for the release of membrane-bound secretory products from various exocrine, endocrine and neural cells1. This has also been shown to be the case in mast cells, which have been used increasingly as a model secretory system2. The secretory granules of mast cells contain several mediators3, some of which, such as histamine, are known to participate in many immune reactions and allergic diseases4,5. Because of mast cell involvement in these clinical syndromes, as well as the role of histamine in gastric acid secretion6 and possibly in brain pathophysiology7, there has been great interest in the pharmacological modulation of histamine release from mast cells8. Serotonin is also stored in mast cell granules of several species but much less is known about its secretion. Because histamine and serotonin may have divergent functions in delayed hypersensitivity4,9, we hypothesized that these amines could undergo differential release. We now report that the tricyclic antidepressant drug amitriptyline (Elavil) inhibits histamine release from stimulated mast cells while permitting the release of serotonin. In these conditions, exocytosis of secretory granules is largely prevented, but serotonin is released by an unknown process which still requires calcium and metabolic energy. The ability to secrete differentially expands the physiological potential of the mast cell, and suggests that release of serotonin may not always indicate mast cell secretion via exocytosis of secretory granules.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Douglas, W. W. Ciba Fdn Symp. 54, 61–90 (1978).
Garland, L. G. & Mongar, J. L. Symp. Soc. exp. Biol. 30, 193–218 (1976).
Ho, P. C., Lewis, R. A., Austen, K. F. & Orange, R. P. Comprehensive Immun. 6, 179–228(1979).
Askenase, P. W. Prog. Allergy 23, 199–320 (1977).
Kazimierczak, W. & Diamant, B. Prog. Allergy 24, 295–365 (1978).
Sell, A. & Walsh, J. H. A. Rev. Physiol. 41, 35–53 (1979).
Green, J. P., Maayani, S., Weinstein, H. & Hough, L. B. Psychopharmac. Bull. 16, 36–38 (1980).
Foreman, J. C. & Lichtenstein, L. M. A. Rev. Med. 31, 181–190 (1980).
Gershon, R. K., Askenase, P. W. & Gershon, M. D. J. exp. Med. 142, 732–747 (1975).
Theoharides, T. C. & Douglas, W. W. Endocrinology 102, 1637–1640 (1978).
Morrison, P. C., Roser, J. F., Henson, P. M. & Cochrane, C. G. J. Immun. 112, 573–582 (1975).
Röhlich, R., Anderson, P. & Uvnäs, B. J. Cell Biol. 51, 465–483 (1971).
Böttcher, J., Hammering, G. & Kapp, J. F. Nature 275, 761–762 (1978).
Nemeth, E. F. & Douglas, W. W. Naunyn-Schmiedebergs Archs Pharmak. 302, 153–163 (1978).
Otsuki, J. A., Grassick, R., Seymour, D. & Kind, L. S. Immun. Commun. 5, 27–39 (1976).
Mazinque, C., Dessaint, J.-P. & Capron, A. J. immun. Meth. 21, 65–77 (1978).
Chasin, M., Scott, C., Shaw, C. & Persico, F. Int. Archs Allergy appl. Immun. 58, 1–10 (1979).
Goldstein, D. J., Finkielman, S. & Nahmond, V. E. Medicine 34, 584–585 (1974).
Miller, P. & Church, M. K. Int. Archs Allergy appl. Immun. 52, 53–58 (1976).
Ichikawa, A., Kaneko, H., Mori, Y. & Tomita, K. Biochem. Pharmac. 26, 197–202 (1977).
Lynch, S. M., Austen, K. F. & Wasserman, S. F. J. Immun. 121, 1394–1399 (1978).
Sannes, P. S. & Spicer, S. S. Am. J. Path. 94, 447–456 (1979).
Calsson, S.-A. & Ritzen, M. Acta physiol. scand. 77, 449–464 (1969).
Gustafsson, B. Int. Archs Allergy appl. Immun. 63, 121–128 (1980).
Tamir, H. & Gershon, M. D. J. Neurochem. 33, 35–44 (1979).
Dvorak, A. M. et al. Lab. Invest. 42, 263–276 (1980).
Tamir, H., Theoharides, T. C., Gershon, M. D. & Askenase, P. W. J. Cell Biol. (in the press).
Lichtenstein, L. M. & Gillepsie, E. J. Pharmac. exp. Ther. 192, 441–450 (1975).
Smith, T. L. & Hauser, G. Biochem. Pharmac. 28, 1759–1763 (1979).
Cockroft, S. & Gomperts, B. D. Biochem. J. 178, 681–687 (1979).
Padawer, J. Am. J. Anat. 141, 299–302 (1974).
Kaliner, M. A. New Engl. J. Med. 501, 498–500 (1979).
Askenase, P. W., Bursztajn, S., Gershon, M. D. & Gershon, R. K. J. exp. Med. 152, 1358–1374 (1980).
Askenase, P. W. & Theoharides, T. C. Fedn Proc. 39, 905 (1980).
Askenase, P. W., Scwhartz, A., Siegel, J. N. & Gershon, R. K. Int. Archs Allergy appl. Immun. 66 (Suppl. 1) 225–233 (1981).
Lawson, D., Fewtrell, C. & Raff, M. C. J. Cell Biol. 79, 394–400 (1978).
Theoharides, T. C. & Douglas, W. W. Science 201, 1143–1145 (1978).
Kremzner, L. T. & Wilson, I. B. Biochim. biophys. Acta 50, 364–367 (1961).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Theoharides, T., Bondy, P., Tsakalos, N. et al. Differential release of serotonin and histamine from mast cells. Nature 297, 229–231 (1982). https://doi.org/10.1038/297229a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/297229a0
This article is cited by
-
Exocytic machineries differentially control mediator release from allergen-triggered RBL-2H3 cells
Inflammation Research (2023)
-
A survey of the currently known mast cell mediators with potential relevance for therapy of mast cell-induced symptoms
Naunyn-Schmiedeberg's Archives of Pharmacology (2023)
-
The Three-Herb Formula Shuang-Huang-Lian stabilizes mast cells through activation of mitochondrial calcium uniporter
Scientific Reports (2017)
-
Mast Cell Accumulation and Degranulation in Rat Bladder with Partial Outlet Obstruction
Advances in Therapy (2015)
-
Mast cell secretory granules: armed for battle
Nature Reviews Immunology (2014)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.