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In this study, we examined the pharmacological action of five
calcium channel blockers (amlodipine, diltiazem, flunarizine,
nifedipine, verapamil) oncompound 48/80 induced prostaglandin D2
and leukotriene C4/D4/E4 biosynthesisof peritoneal mast cell.
Our data have indicated that preincubation of fivecalcium
channel blockers possessed variant inhibitory effects on
compound48/80 induced leukotrienes C4/D4/E4 and prostaglandin D2
biosynthesis from mastcells. In comparison, the inhibitory
effect of amlodipine on leukotrienesC4/D4/E4 biosynthesis is
more significant. And flunarizine inhibit prostaglandinD2
biosynthesis is more significant.
In order to determine the role of calcium channel blockers on
mediated secretion, the intracellular c-AMP and c-GMP levels of
mast cell were measure by Amersham EIA kit. Calcium channel
blockers exhibited concentration-dependentmanner to increase of
these intracellular secondary messengers. Among fivecalcium
channel blockers, flunarizine has shown a potent effect in the
increaseof intracellular c-GMP level. And amlodipine exhibit a
significant effect inthe increase of intracellular c-AMP
level. And the modification of IP3 levelwas determined by Du-
Pont RIA kit. Calcium channel blockers exhibited dose-dependent
inhibitory effect on IP3 generation. In comparison, amlodipine
and nifedipine possess a more significant inhibitory effect on
the IP3 generation.In this study, we further characterized the
mechanisms that regulate theactivation of rat mast cells
response to calcium channel blocker. We suggestedthat calcium
channel blockers may through modulate intracellular
secondarymessenger (IP3, c-AMP, c-GMP) pathway to influence
leukotrienes C4/D4/E4 andprostaglandin D2 biosynthesis on rat
peritoneal mast cell.
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