The role of cyclic AMP and protein kinase A in stimulation of neutrophil migration by endothelins.
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-1) 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-1, 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.
Elferink
J G
JG
Department of Medical Biochemistry, University of Leiden, The Netherlands.
de Koster
B M
BM
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D002227:Carbazoles; D002465:Cell Movement / Q000187:drug effects*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D019332:Endothelin-1 / Q000494:pharmacology; D019333:Endothelin-2 / Q000494:pharmacology; D019334:Endothelin-3 / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007097:Imines / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D002227:Carbazoles; D019332:Endothelin-1; D019333:Endothelin-2; D019334:Endothelin-3; D016232:Endothelins; D004791:Enzyme Inhibitors; D007097:Imines; D007211:Indoles; D011758:Pyrroles; D013873:Thionucleotides; C074155:8-chloroadenosine-3',5'-cyclic monophosphorothioate; C017759:9-(tetrahydro-2-furyl)-adenine; C016957:adenosine-3',5'-cyclic phosphorothioate; C057416:KT 5720; C014925:RMI 12330A; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000225:Adenine