TY - JOUR
T1 - Serotonin and its 5-HT1 receptor in human mastocytosis
AU - Ritter, Markus
AU - El-Nour, Husameldin
AU - Hedblad, Mari Anne
AU - Butterfield, Joseph H.
AU - Beck, Olof
AU - Stephanson, Niclaus
AU - Holst, Mikael
AU - Giscombe, Ricardo
AU - Azmitia, Efrain C.
AU - Nordlind, Klas
N1 - Funding Information:
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.
PY - 2012/8
Y1 - 2012/8
N2 - 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 10-810-10 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.
AB - 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 10-810-10 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.
KW - Human
KW - Mast cell
KW - Mastocytosis
KW - Receptor
KW - Serotonin
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U2 - 10.3109/08923973.2011.651222
DO - 10.3109/08923973.2011.651222
M3 - Article
C2 - 22268664
AN - SCOPUS:84863789023
SN - 0892-3973
VL - 34
SP - 679
EP - 685
JO - Immunopharmacology and Immunotoxicology
JF - Immunopharmacology and Immunotoxicology
IS - 4
ER -