PMID- 12595089 OWN - NLM STAT- MEDLINE DCOM- 20030708 LR - 20190610 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1620 IP - 1-3 DP - 2003 Mar 17 TI - Inhibition of formyl-methionyl-leucyl-phenylalanine-stimulated phospholipase D activation in rat neutrophils by the synthetic isoquinoline DMDI. PG - 191-8 AB - The expression of phospholipase D (PLD) isoenzymes in neutrophils was investigated using reverse transcription-polymerase chain reaction analysis. Amplification products of predicted size were obtained from rat neutrophils with nucleotide sequences corresponding to PLD1a and PLD2. 1-(3',4'-Dimethoxybenzyl)-6,7-dichloroisoquinoline (DMDI) inhibited the formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated PLD activation in rat neutrophils. The underlying cellular signaling mechanism of DMDI inhibition was investigated. The fMLP-induced protein tyrosine phosphorylation and the membrane translocation of ADP-ribosylation factor (ARF) and Rho A in neutrophils was attenuated by DMDI in a concentration-dependent manner. However, neither the membrane association of protein kinase C-alpha and -beta isoenzymes in fMLP-stimulated cells nor the GTPgammaS- and phorbol 12-myristate 13-acetate-stimulated membrane translocation of ARF and Rho A in a cell-free system was affected significantly by DMDI. These results indicate that the expression of PLD1a and PLD2 mRNA in neutrophils. Attenuation of protein tyrosine phosphorylation and the membrane association of ARF and Rho A probably play a concerted role in the inhibition of PLD by DMDI in rat neutrophils in response to fMLP. FAU - Chang, Ling-Chu AU - Chang LC AD - Department of Education and Research, Taichung Veterans General Hospital, 160, Chung Kang Road, Sec. 3, Taiwan, ROC. FAU - Chen, Chi-Ming AU - Chen CM FAU - Wang, Jih-Pyang AU - Wang JP LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (1-(3',4'-dimethoxybenzyl)-6,7-dichloroisoquinoline) RN - 0 (Enzyme Inhibitors) RN - 0 (Isoenzymes) RN - 0 (Isoquinolines) RN - 0 (RNA, Messenger) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 3.1.4.4 (Phospholipase D) RN - EC 3.6.5.2 (ADP-Ribosylation Factor 1) RN - EC 3.6.5.2 (rhoA GTP-Binding Protein) SB - IM MH - ADP-Ribosylation Factor 1/metabolism MH - Animals MH - Cell Membrane/drug effects/enzymology MH - Cell-Free System MH - Enzyme Activation/drug effects MH - Enzyme Inhibitors/pharmacology MH - Isoenzymes/antagonists & inhibitors/metabolism MH - Isoquinolines/*pharmacology MH - N-Formylmethionine Leucyl-Phenylalanine MH - Neutrophils/drug effects/*enzymology MH - Phospholipase D/*antagonists & inhibitors/metabolism MH - Phosphorylation/drug effects MH - Protein Kinase C/metabolism MH - RNA, Messenger/analysis MH - Rats MH - Reverse Transcriptase Polymerase Chain Reaction MH - rhoA GTP-Binding Protein/metabolism EDAT- 2003/02/22 04:00 MHDA- 2003/07/09 05:00 CRDT- 2003/02/22 04:00 PHST- 2003/02/22 04:00 [pubmed] PHST- 2003/07/09 05:00 [medline] PHST- 2003/02/22 04:00 [entrez] AID - S0304416502005329 [pii] AID - 10.1016/s0304-4165(02)00532-9 [doi] PST - ppublish SO - Biochim Biophys Acta. 2003 Mar 17;1620(1-3):191-8. doi: 10.1016/s0304-4165(02)00532-9.