Substance P-related inhibitors of mast cell exocytosis act on G-proteins or on the cell surface

被引:23
作者
Chahdi, A [1 ]
Mousli, M [1 ]
Landry, Y [1 ]
机构
[1] Univ Louis Pasteur Strasbourg 1, Fac Pharm, INSERM U425, Lab Neuroimmunopharmacol, F-67401 Illkirch Graffenstaden, France
关键词
mast cell; G protein; D-Pro(4),D-Trp(7,9,10)]substance P-(4-11); p-Glu(4),D-Trp(7,9,10)]substance P-(5-11); mastoparan; GTPase activity;
D O I
10.1016/S0014-2999(97)01480-5
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
[p-Glu(5), D-Trp(7,9,10)]substance P-(5-11) inhibited mastoparan-stimulated GTPase activity in homogenized rat peritoneal mast cells and decreased histamine secretion induced by mastoparan from streptolysin O-permeabilized mast cells (IC50 of about 30 mu M), but not from intact cells. In contrast, [D-Pro(4), D-Trp(7,9,10)]substance P-(4-11) inhibited the secretion from intact cells (IC(5)0 of about 10 mu M) but had no effect on histamine secretion from permeabilized cells, suggesting that this peptide exerts its inhibitory effect on the plasma membrane, whereas [p-Glu(5), D-Trp(7,9,10)]substance P-(5-11) interacts with G proteins. Pretreatment of mast cells with neuraminidase led to an inhibition of the secretory response to mastoparan and related triggers. This response was restored following cell permeabilization, demonstrating the role of the cell surface on the entry of mastoparan and related triggers and on their ability to reach G proteins sensitive to pertussis toxin and [p-Glu(5), D-Trp(7,9,10)]substance P-(5-11). (C) 1998 Elsevier Science B.V.
引用
收藏
页码:329 / 335
页数:7
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