文章基本信息

标题：Differential Effects of β2-Adrenoceptor Desensitization on the IgE-Dependent Release of Chemical Mediators from Cultured Human Mast Cells
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作者：Toshikazu Tsuji ; Toshinobu Kato ; Masahiro Kimata 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2004
卷号：27
期号：10
页码：1549-1554
DOI：10.1248/bpb.27.1549
出版社：The Pharmaceutical Society of Japan
摘要：In the present study, we examined the inhibitory effects of the β₂-adrenoceptor agonists isoproterenol, salbutamol, fenoterol, and clenbuterol, on the release of chemical mediators from cultured human mast cells after prolonged treatment with the agonists. Although preincubation of sensitized mast cells for 10 min with β₂-adrenoceptor agonists potently inhibited mediator release, prolongation of the preincubation period up to 240 min attenuated the inhibition. The attenuation of histamine release inhibition was potent when compared with that of prostaglandin D₂ (PGD₂) and cysteinyl leukotriene (LT) release inhibition. In contrast, forskolin inhibited mediator release and the inhibition increased gradually in proportion to the preincubation period. The reduced inhibition by the β₂-adrenoceptor agonists was compensated for by simultaneous treatment with cholera toxin. The β₂-adrenoceptor agonists elevated intracellular cAMP levels after 10-min incubation and the elevated levels were almost comparable to those after 240-min incubation. Forskolin elevated the intracellular cAMP levels more potently after incubation for 240 min than after 10 min. When mast cells were incubated for 3 d with the β₂-adrenoceptor agonists, similar attenuation of mediator release inhibition was observed. Elevation of intracellular cAMP levels was also attenuated, although β₂-adrenoceptor mRNA expression was potentiated. The present results collectively indicate that the attenuation of mediator release inhibition by β₂-adrenoceptor agonists under the present experimental conditions involves uncoupling between β₂-adrenoceptors and Gs proteins. Furthermore, the β₂-adrenoceptor desensitization causes differential attenuating effects on the inhibition of histamine, PGD₂, and LT release, suggesting that downstream events involved in each inhibitory pathway have different sensitivity to receptor desensitization.
关键词：β2-adrenoceptor agonist;desensitization;human cultured mast cell;IgE;chemical mediator