PMID- 11755159
OWN - NLM
STAT- MEDLINE
DCOM- 20020725
LR  - 20190624
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 434
IP  - 1-2
DP  - 2002 Jan 2
TI  - Cellular mechanisms of inhibition of superoxide anion generation in rat 
      neutrophils by the synthetic isoquinoline DMDI.
PG  - 9-16
AB  - This study was undertaken to assess the cellular localization of the inhibitory 
      effect of a chemically synthetic isoquinoline compound 
      1-(3',4'-dimethoxybenzyl)-6,7-dichloroisoquinoline (DMDI) on the 
      formyl-methionyl-leucyl-phenylalanine (fMLP)-induced respiratory burst in rat 
      neutrophils. The DMDI concentration dependently inhibited the superoxide anion 
      (O(2)(*-)) generation and O(2) consumption (IC(50) 12.2+/-4.9 and 15.2+/-8.4 
      microM, respectively) of neutrophils. DMDI did not scavenge the O(2)(*-) 
      generated during the autoxidation of dihydroxyfumaric acid in a cell-free system. 
      DMDI did not elevate cellular cyclic AMP levels. Inhibition of O(2)(*-) 
      generation by DMDI in neutrophils was not reversed by a cyclic AMP-dependent 
      protein kinase inhibitor, 
      (8R,9S,11S)-(-)-9-hydroxy-9-hexoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo[a,g]cycloocta[cde]trinden-1-one 
      (KT5720). The DMDI concentration dependently inhibited the late plateau phase but 
      not the initial spike of fMLP-induced [Ca(2+)](i) changes in the presence of 
      extracellular Ca(2+). However, DMDI had no effect on the fMLP-induced [Ca(2+)](i) 
      changes in the absence of extracellular Ca(2+). In addition, DMDI did not affect 
      the fMLP-stimulated phosphatidylinositol 3-kinase (PI3-kinase) activation. DMDI 
      produced a concentration-dependent reduction in the formation of phosphatidic 
      acid and phosphatidylethanol in the presence of ethanol from fMLP-stimulated 
      neutrophils (IC(50) 13.3+/-4.0 and 9.4+/-4.3 microM, respectively). On the basis 
      of the immunoblot analysis of the phosphorylation of the mitogen-activated 
      protein (MAP) kinase, DMDI attenuated the fMLP-stimulated MAP kinase 
      phosphorylation in a similar concentration range. Collectively, these results 
      indicate that the inhibition of the respiratory burst by DMDI in rat neutrophils 
      is mediated through the blockade of phospholipase D and MAP kinase signaling 
      pathways.
FAU - Wang, Jih-Pyang
AU  - Wang JP
AD  - Department of Education and Research, Taichung Veterans General Hospital, 
      Taichung, Taiwan, ROC. w1994@vghtc.vghtc.gov.tw
FAU - Chang, Ling-Chu
AU  - Chang LC
FAU - Raung, Shue-Ling
AU  - Raung SL
FAU - Hsu, Mei-Feng
AU  - Hsu MF
FAU - Chen, Chi-Ming
AU  - Chen CM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (1-(3',4'-dimethoxybenzyl)-6,7-dichloroisoquinoline)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Isoquinolines)
RN  - 11062-77-4 (Superoxides)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.1.4.4 (Phospholipase D)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Calcium/metabolism
MH  - Cyclic AMP/physiology
MH  - Isoquinolines/*pharmacology
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/*drug effects/metabolism
MH  - Phosphatidylinositol 3-Kinases/physiology
MH  - Phospholipase D/metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Superoxides/*metabolism
EDAT- 2002/01/05 10:00
MHDA- 2002/07/26 10:01
CRDT- 2002/01/05 10:00
PHST- 2002/01/05 10:00 [pubmed]
PHST- 2002/07/26 10:01 [medline]
PHST- 2002/01/05 10:00 [entrez]
AID - S0014299901015369 [pii]
AID - 10.1016/s0014-2999(01)01536-9 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2002 Jan 2;434(1-2):9-16. doi: 10.1016/s0014-2999(01)01536-9.