Diacylglycerol kinase inhibitor, R59022, potentiates neutrophil oxidase activation by Ca2+-dependent stimuli. Evidence for two separate but convergent pathways.
An inhibitor of diacylglycerol kinase, R59022, enhanced activation of the neutrophil oxidase stimulated by the Ca2+-ionophore, A23187 (1 microM), and by N-formyl-methionyl leucyl-phenylalanine (1 microM). The enhancement was reversed by two inhibitors of c-kinase, retinal (10 microM), and gossypol (20 microM). Activation by phorbol-myristyl-acetate and unopsonised latex beads were not enhanced. It was concluded that the chemotactic peptide generated diacylglycerol, but that maximum activation of c-kinase by this route was not achievable. The role of diacylglycerol in activation by beads remained unclear.
Cooke
E
E
University Department of Surgery, University of Wales College of Medicine, Cardiff, U.K.
Al-Mohanna
F A
FA
Hallett
M B
MB
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D019852:Diacylglycerol Kinase; D004789:Enzyme Activation / Q000187:drug effects; D006072:Gossypol / Q000494:pharmacology; D008163:Luminescent Measurements; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D010088:Oxidoreductases / Q000032:analysis*; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D011493:Protein Kinase C / Q000502:physiology; D011744:Pyrimidinones / Q000494:pharmacology*; D051381:Rats; D013844:Thiazoles / Q000494:pharmacology*
D011744:Pyrimidinones; D013844:Thiazoles; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; C047505:R 59022; D010088:Oxidoreductases; D010770:Phosphotransferases; D019852:Diacylglycerol Kinase; D011493:Protein Kinase C; D006072:Gossypol; D002118:Calcium