Serotonin and its 5-HT1 receptor in human mastocytosis

Immunopharmacol Immunotoxicol. 2012 Aug;34(4):679-85. doi: 10.3109/08923973.2011.651222. Epub 2012 Feb 1.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Adult
  • Cell Line
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / immunology*
  • Humans
  • Male
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • Mast Cells / pathology
  • Mastocytosis, Cutaneous
  • Middle Aged
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / immunology*
  • Receptor, Serotonin, 5-HT1A / biosynthesis
  • Receptor, Serotonin, 5-HT1A / immunology*
  • Serotonin / immunology*
  • Serotonin / metabolism
  • Serotonin Receptor Agonists / pharmacology
  • Skin / immunology*
  • Skin / metabolism
  • Skin / pathology
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Tumor Cells, Cultured

Substances

  • Neoplasm Proteins
  • Serotonin Receptor Agonists
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • 8-Hydroxy-2-(di-n-propylamino)tetralin