Influence of mizolastine on antigen-induced activation of signalling pathways in murine mast cells.
BACKGROUND
There is accumulating evidence that some antihistamines can interrupt intermediate signalling events that regulate cell function. The effect of mizolastine on both the generation and release process of many cytokines in mast cells further implies that the inhibition by mizolastine may target signalling pathways.


OBJECTIVE
To observe the influence of mizolastine on antigen-induced activation of signalling pathways in murine mast cells.


METHODS
Western blot analysis and enzyme assay were performed. Immunoblots were prepared from whole cell lysates and probed with antibodies against Fyn, Akt, ERK, p38, phospho-Fyn, phospho-Akt, phospho-ERK and phospho-p38, respectively.


RESULTS
Our study showed that signalling molecules such as IP3, Fyn, p38 and ERK were enhanced when mast cells were stimulated by antigen, and that this was not inhibited by treatment with mizolastine. Mizolastine at concentrations from 10(-9) to 10(-5) mol/L could inhibit activation of the PI3K kinase downstream signalling molecule Akt to antigen stimulation. The study also demonstrated that mizolastine exerted inhibitory ability on protein kinase C (PKC) activation in a dose-dependent manner.


CONCLUSIONS
PKC-mediated phosphorylation of Akt can be blocked by mizolastine. There may be a PKC-independent pathway effectively activating MAPK pathways in mast cells in response to antigen induction, which cannot be affected by mizolastine.
Xia
Q
Q
Department of Biochemistry, Anhui Medical University, Hefei, China.
Zhou
W M
WM
Yang
S
S
Zhang
S Q
SQ
Chen
B
B
Wang
D B
DB
Wang
Y
Y
Zhang
X J
XJ
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects*; D051379:Mice; D011493:Protein Kinase C / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects; D051076:Proto-Oncogene Proteins c-fyn / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects
D001562:Benzimidazoles; D006634:Histamine H1 Antagonists; C076170:mizolastine; D015544:Inositol 1,4,5-Trisphosphate; D051076:Proto-Oncogene Proteins c-fyn; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases