The role of cyclic AMP and protein kinase A in stimulation of neutrophil migration by endothelins

被引：9

作者：

Elferink, JGR ^{[1
]}

de Koster, BM ^{[1
]}

机构：

[1] Leiden Univ, Dept Med Biochem, NL-2300 RA Leiden, Netherlands

来源：

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY | 1998年 / 358卷 / 05期

关键词：

neutrophil; endothelins; chemotaxis; migration; cAMP; protein kinase A;

D O I：

10.1007/PL00005287

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The role of cAMP and cAMP-dependent protein kinase A (PKA) in endothelin (ET)-stimulated migration of human neutrophils was studied. Endothelins caused an increase in neutrophil migration when they were applied in low (nanomolar) concentrations; stimulation of migration was either predominantly chemokinetic (ET-I) or chemotactic (ET-2, ET-3). All endothelins, at concentrations which gave maximal stimulation of migration, caused an increase of cAMP level. Two inhibitors of adenylate cyclase, MDL-12330A and SQ-22536, completely inhibited migration activated by ET-I, ET-2 or ET-3, indicating that cAMP generation played a decisive role in endothelin-activated migration. The role of PKA in endothelin-activated migration was considered. Two specific antagonists of PKA strongly inhibited endothelin-activated migration. KT-5720, an inhibitor of PKA, also inhibited ET-activated migration, but only when electroporated cells were used. The results suggest that the effect of cAMP on endothelin-activated migration was mediated by PKA.

引用

页码：518 / 521

页数：4

共 22 条

[1] NEUTROPHIL CHEMOTAXIS INDUCED BY THE DIACYLGLYCEROL KINASE INHIBITOR R59022 [J].

BOONEN, GJJC ;

DEKOSTER, BM ;

VANSTEVENINCK, J ;

ELFERINK, JGR .

BIOCHIMICA ET BIOPHYSICA ACTA, 1993, 1178 (01) :97-102

[2] CHEMOTACTIC EFFECT OF MIXTURES OF ANTIBODY AND ANTIGEN ON POLYMORPHONUCLEAR LEUCOCYTES [J].

BOYDEN, S .

JOURNAL OF EXPERIMENTAL MEDICINE, 1962, 115 (03) :453-&

[3] EFFECTS OF SELECTIVE-INHIBITION OF PROTEIN-KINASE-C, CYCLIC-AMP-DEPENDENT PROTEIN-KINASE, AND CA2+-CALMODULIN-DEPENDENT PROTEIN-KINASE ON NEURITE DEVELOPMENT IN CULTURED RAT HIPPOCAMPAL-NEURONS [J].

CABELL, L ;

AUDESIRK, G .

INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, 1993, 11 (03) :357-368

[4] EFFECT OF CAMP AND CGMP ON ENDOTHELIN-STIMULATED TYROSINE PHOSPHORYLATION IN RABBIT PLATELETS [J].

CATALAN, RE ;

MARTINEZ, AM ;

GARGIULO, L ;

LIRAS, A .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1995, 215 (01) :219-226

[5]

ELFERINK JGR, 1995, J CARDIOVASC PHARM, V26, pS142

[6] The stimulation of human neutrophil migration by angiotensin II: Its dependence on Ca2+ and the involvement of cyclic GMP [J].

Elferink, JGR ;

deKoster, BM .

BRITISH JOURNAL OF PHARMACOLOGY, 1997, 121 (04) :643-648

[7] ENDOTHELIN-INDUCED ACTIVATION OF NEUTROPHIL MIGRATION [J].

ELFERINK, JGR ;

DEKOSTER, BM .

BIOCHEMICAL PHARMACOLOGY, 1994, 48 (05) :865-871

[8] THE EFFECT OF CYCLIC-GMP AND CYCLIC-AMP ON MIGRATION BY ELECTROPORATED HUMAN NEUTROPHILS [J].

ELFERINK, JGR ;

DEKOSTER, BM .

EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION, 1993, 246 (02) :157-161

[9] The effect of endothelin-2 (Et-2) on migration and changes in cytosolic free calcium of neutrophils [J].

Elferink, JGR ;

deKoster, BM .

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1996, 353 (02) :130-135

[10] The role of cyclic nucleotides in neutrophil migration [J].

Elferink, JGR ;

VanUffelen, BE .

GENERAL PHARMACOLOGY-THE VASCULAR SYSTEM, 1996, 27 (02) :387-393

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