Inhibition of superoxide anion production by extracellular acidification in neutrophils.
Extracellular acidification inhibited formyl-Met-Leu-Phe- or C5a-induced superoxide anion (O(2)(-)) production in differentiated HL-60 neutrophil-like cells and human neutrophils. A cAMP-increasing agonist, prostaglandin E(1), also inhibited the formyl peptide-induced O(2)(-) production. The inhibitory action on the O(2)(-) production by extracellular acidic pH was associated with cAMP accumulation and partly attenuated by H89, a protein kinase A inhibitor. A significant amount of mRNAs for T-cell death-associated gene 8 (TDAG8) and other proton-sensing ovarian cancer G-protein-coupled receptor 1 (OGR1)-family receptors is expressed in these cells. These results suggest that cAMP/protein kinase A, possibly through proton-sensing G-protein-coupled receptors, may be involved in extracellular acidic pH-induced inhibition of O(2)(-) production.
Murata
Naoya
N
Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation Gunma University, Showa-machi, Maebashi, Japan.
Mogi
Chihiro
C
Tobo
Masayuki
M
Nakakura
Takashi
T
Sato
Koichi
K
Tomura
Hideaki
H
Okajima
Fumikazu
F
D000527:Alprostadil / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000378:metabolism; D015936:Complement C5a / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007155:Immunologic Factors / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D013481:Superoxides / Q000037:antagonists & inhibitors* / Q000378:metabolism
D018797:Cell Cycle Proteins; D005343:Fibrinolytic Agents; C115270:G2A receptor; C091670:GPR4 protein, human; C513334:GPR65 protein, human; C486281:GPR68 protein, human; D007155:Immunologic Factors; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D043562:Receptors, G-Protein-Coupled; D013449:Sulfonamides; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000527:Alprostadil; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide