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Abstract
Context: Human mastocytosis is a rare disease, in which the serotonergic system may be involved.
Objective: The objective of the present study was to examine the possible presence of serotonin (5-HT) and its 5-HT1A receptor (R) in the skin of patients with mastocytosis. In addition, the effect of the 5-HT1AR was tested on human mastocytosis cells, cultured in vitro.
Materials and methods: The expression of 5-HT and 5-HT1AR in patients with urticaria pigmentosa and mastocytoma was studied using immunohistochemistry. The effects of 8-OH-DPAT, an agonist of 5-HT1AR, on the proliferation (cell number), viability, apoptosis, spontaneous release of histamine, as well as a possible 5-HT metabolism, in the human HMC-1 mast cell line, were investigated.
Results: Both 5-HT and 5-HT1AR were expressed in the mast cells in biopsies of mastocytoma and urticaria pigmentosa, as well as in HMC-1 cells. However, no metabolism of 5-HT by the cell line could be detected by the methodology used. The 5-HT1AR agonist had no significant effect on the viability and number of HMC-1 cells, and was without effect on the apoptosis. At concentrations of 10−6 mol/L and 10−8 –10−10 mol/L (i.e. also at physiological concentrations), the agonist inhibited histamine release by these cells by as much as 30%.
Conclusion: These findings indicate that 5-HT and its 5-HT1AR are expressed in human mastocytosis and that an agonist of the 5-HT1AR might be of value in the treatment of these patients.
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Acknowledgments
The technical assistance of Mrs. Anna-Lena Kastman is gratefully acknowledged. The present investigation was supported financially by grants from the Welander/Finsen Foundation and the Karolinska Institutet.
Declaration of interest
M.H. is a full time contractor with Pfizer Inc.