Involvement of arachidonic acid in nonimmunologic production of superoxide in mast cells.
BACKGROUND
A number of different molecules are known to be involved in the signal pathway to release histamine from mast cells, among which arachidonic acid (AA) is one of the key mediators. On the other hand, we found that the application of compound 48/80, a typical histamine liberator, generated superoxide in mast cells. In the present study, we investigated the mechanism of superoxide production in mast cells with respect to AA signaling in conjunction with a fine structural analysis.


METHODS
Superoxide production was monitored by chemiluminescence in rat peritoneal mast cells and their subfractions after various treatments. For scanning electron micrography, the conditions for fixation and freeze-fracture were optimized to get natural fine images.


RESULTS
Compound 48/80 induced superoxide production in the isolated mast cells and some of their subfractions possibly through intracellular increase in Ca(2+) concentration, activation of cytosolic phospholipase A(2), and release of AA.


CONCLUSIONS
The present results indicate the critical role of AA in the signal pathway to generate superoxide from mast cells in response to compound 48/80.
Sakaguchi
Masakiyo
M
Department of Pharmacology, Faculty of Pharmaceutical Science, Tokushimabunri University, Tokushima, Japan. sakaguchi_masa@yahoo.co.jp
Fukuishi
Nobuyuki
N
Teramoto
Kazuyo
K
Miyazaki
Masahiro
M
Huh
Nam-ho
NH
Namba
Masayoshi
M
Akagi
Masaaki
M
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013481:Superoxides / Q000378:metabolism*
D017442:Histamine Agonists; D013481:Superoxides; D016718:Arachidonic Acid