A new semisynthetic butenolide inhibits mast cell activation induced by the calcium ionophore A23187

PENISSI AB; MARIANI ML; RUDOLPH MI; PIEZZI RS

Copper Mountain, Colorado USA

Simposio; Keystone Symposia. Mast cells, basophils and IgE: host defense and disease.; 2007

Keystone Center,Colorado

In previous work we have demonstrated that a new semisynthetic butenolide with antiulcer properties (3-benzyloxymethyl-5H-furan- 2-one; But), inhibits mast cell exocytosis induced by the G protein stimulant compound 48/80. The present work examines the effect of But on mast cell degranulation induced by the calcium ionophore A23187, to determine whether But acts upstream or downstream of cytosolic calcium increase. Rat peritoneal mast cells were purified in Percoll and incubated with: 1) Tyrode solution or 2) A23187 or 3) But+A23187. Serotonin release studies by high performance liquid chromatography (HPLC), evaluation of mast cell morphology by light microscopy, dose-response and time-response studies, cell viability evaluation by the tripan blue dye exclusion, comparative studies with ketotifen (Ket), and drug stability evaluation by thin layer chromatography (TLC) were carried out. Calcium ionophore increased serotonin release from mast cells and elicited evident morphological changes. These effects were inhibited by But in a dose- and time-dependent manner. The inhibitory effect exhibited by But was stronger than that of ketotifen, a classical mast cell stabilizer. In conclusion, the present study demonstrates that But inhibits A23187-induced mast cell activation, acting downstream of cytosolic calcium increase. In previous work we have demonstrated that a new semisynthetic butenolide with antiulcer properties (3-benzyloxymethyl-5H-furan- 2-one; But), inhibits mast cell exocytosis induced by the G protein stimulant compound 48/80. The present work examines the effect of But on mast cell degranulation induced by the calcium ionophore A23187, to determine whether But acts upstream or downstream of cytosolic calcium increase. Rat peritoneal mast cells were purified in Percoll and incubated with: 1) Tyrode solution or 2) A23187 or 3) But+A23187. Serotonin release studies by high performance liquid chromatography (HPLC), evaluation of mast cell morphology by light microscopy, dose-response and time-response studies, cell viability evaluation by the tripan blue dye exclusion, comparative studies with ketotifen (Ket), and drug stability evaluation by thin layer chromatography (TLC) were carried out. Calcium ionophore increased serotonin release from mast cells and elicited evident morphological changes. These effects were inhibited by But in a dose- and time-dependent manner. The inhibitory effect exhibited by But was stronger than that of ketotifen, a classical mast cell stabilizer. In conclusion, the present study demonstrates that But inhibits A23187-induced mast cell activation, acting downstream of cytosolic calcium increase. 2-one; But), inhibits mast cell exocytosis induced by the G protein stimulant compound 48/80. The present work examines the effect of But on mast cell degranulation induced by the calcium ionophore A23187, to determine whether But acts upstream or downstream of cytosolic calcium increase. Rat peritoneal mast cells were purified in Percoll and incubated with: 1) Tyrode solution or 2) A23187 or 3) But+A23187. Serotonin release studies by high performance liquid chromatography (HPLC), evaluation of mast cell morphology by light microscopy, dose-response and time-response studies, cell viability evaluation by the tripan blue dye exclusion, comparative studies with ketotifen (Ket), and drug stability evaluation by thin layer chromatography (TLC) were carried out. Calcium ionophore increased serotonin release from mast cells and elicited evident morphological changes. These effects were inhibited by But in a dose- and time-dependent manner. The inhibitory effect exhibited by But was stronger than that of ketotifen, a classical mast cell stabilizer. In conclusion, the present study demonstrates that But inhibits A23187-induced mast cell activation, acting downstream of cytosolic calcium increase.