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The effects of cromakalim on the mediator releases from guinea pig lung mast cell activated by specific antigen-antibody reactions

Authors
 Jai Youl Ro  ;  Young Nae Yim  ;  Kyung Hwan Kim 
Citation
 YONSEI MEDICAL JOURNAL, Vol.37(5) : 325-338, 1996-10 
Journal Title
YONSEI MEDICAL JOURNAL
ISSN
 0513-5796 
Issue Date
1996-10
MeSH
Adenylyl Cyclases / metabolism ; Animals ; Antigen-Antibody Reactions* ; Benzopyrans / pharmacology* ; Cromakalim ; Diglycerides / biosynthesis ; Female ; Guinea Pigs ; Histamine Release / drug effects* ; Leukotrienes / metabolism* ; Lung / drug effects ; Lung / metabolism ; Mast Cells / drug effects* ; Mast Cells / metabolism ; Methylation ; Phospholipase D / metabolism ; Phospholipids / metabolism ; Potassium Channels / drug effects* ; Pyrroles / pharmacology*
Abstract
The inhibitory effect of cromakalim on the mediator release from mast cells caused by antigenantibody reactions was in controversy with the specific antigen used. However, it has recently been observed that cromakalim inhibits the release of mediators from superfused tracheal and parenchymal strips or lung mast cells after passive sensitization with the IgG1 antibody. An attempt, therefore, was made to determine the inhibitory mechanisms of cromakalim on the release of mediators such as histamine and leukotriene released by the activation of enzymes during mast cell activation. Guinea pig lung mast cells were purified through enzyme digestion, rough percoll and continuous percoll density gradients. The purified mast cells were prelabeled with [3H]palmitic acid. PLD activity was assessed more directly by the production of labeled phosphatidylethanol by PLD-mediated transphosphatidylation in the presence of ethanol. In the cells labelled with [3H]myristic acid, [3H] DAG production was measured. The methyltransferase activity was assessed by measuring the incorporation of [3H]methyl moiety into phospholipids in sensitized mast cells labelled with L-[3H] methylmethionine. cAMP level was measured by radioimmunoassay. Cromakalim resulted in a decrease in the amount of histamine and leukotrienes releases by 30% in the ovalumin-induced mast cell. Cromakalim had little effect on phospholipase D activity enhanced by the activated mast cell. Cromakalim inhibited the initial increase of diacylglycerol production during mast cell activations. Cromakalim inhibited the phospholipid methylation increased in the activated mast cell. These results show that cromakalim decreases histamine release by inhibiting the initial increase of 1,2-diacylglycerol during the mast cell activation, which is mediated via the phosphatidylinositide-phospholipase C system rather than the phosphatidylcholine-phospholipase D system. Furthermore, cromakalim reduces phosphatidylcholine production by inhibiting the methyltransferase, which decreases the conversion of phosphatidylcholine into arachidonic acid and inhibits the production of leukotrienes.
Files in This Item:
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DOI
10.3349/ymj.1996.37.5.325
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Hwan(김경환)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/183432
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