PMID- 10591142
OWN - NLM
STAT- MEDLINE
DCOM- 19991222
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 58
IP  - 12
DP  - 1999 Dec 15
TI  - Effects of local anesthetics on phospholipase D activity in differentiated human 
      promyelocytic leukemic HL60 cells.
PG  - 1881-9
AB  - Local anesthetics impair certain functions of neutrophils, and phospholipase D 
      (PLD) is considered to play an important role in the regulation of these 
      functions. To understand the mechanisms by which local anesthetics suppress the 
      functions of neutrophils, we examined the effects of local anesthetics on PLD in 
      neutrophil-like differentiated human promyelocytic leukemic HL60 cells. 
      Tetracaine, a local anesthetic, inhibited formyl-methionyl-leucyl-phenylalanine 
      (fMLP)- and 4beta-phorbol 12-myristate 13-acetate (PMA)-induced PLD activation, 
      but potentiated fMLP-stimulated phospholipase C activity. All four local 
      anesthetics tested suppressed PMA-induced PLD activation to different extents, 
      and the order of their potency was tetracaine > bupivacaine > lidocaine > 
      procaine. In a cell-free system, tetracaine suppressed guanosine 
      5'-O-(3-thiotriphosphate) (GTPgammaS)-induced PLD activation as well as 
      PMA-induced PLD activation. Western blot analysis revealed that tetracaine 
      prevented the membrane translocation of PLD-activating factors, ADP-ribosylation 
      factor, RhoA, and protein kinase Calpha. Tetracaine also inhibited the activity 
      of recombinant hPLD1a in vitro. These results suggest that local anesthetics 
      suppress PLD activation in differentiated HL60 cells by preventing the membrane 
      translocation of PLD-activating factors, and/or by directly inhibiting the enzyme 
      per se. Therefore, it could be assumed that local anesthetics would suppress the 
      functions of neutrophils by inhibition of PLD activation.
FAU - Tan, Z
AU  - Tan Z
AD  - Department of Anesthesiology and Critical Care Medicine, Gifu University School 
      of Medicine, Japan.
FAU - Dohi, S
AU  - Dohi S
FAU - Ohguchi, K
AU  - Ohguchi K
FAU - Nakashima, S
AU  - Nakashima S
FAU - Banno, Y
AU  - Banno Y
FAU - Ono, Y
AU  - Ono Y
FAU - Nozawa, Y
AU  - Nozawa Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Anesthetics, Local)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Recombinant Proteins)
RN  - 0619F35CGV (Tetracaine)
RN  - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate))
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - EC 3.1.4.4 (Phospholipase D)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Anesthetics, Local/*pharmacology
MH  - Biological Transport/drug effects
MH  - Cell Differentiation
MH  - Cell Membrane/metabolism
MH  - Drug Synergism
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology
MH  - HL-60 Cells
MH  - Humans
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/*drug effects/physiology
MH  - Phospholipase D/antagonists & inhibitors/*metabolism
MH  - Recombinant Proteins/antagonists & inhibitors
MH  - Tetracaine/*pharmacology
MH  - Tetradecanoylphorbol Acetate/pharmacology
EDAT- 1999/12/11 00:00
MHDA- 1999/12/11 00:01
CRDT- 1999/12/11 00:00
PHST- 1999/12/11 00:00 [pubmed]
PHST- 1999/12/11 00:01 [medline]
PHST- 1999/12/11 00:00 [entrez]
AID - S0006-2952(99)00283-X [pii]
AID - 10.1016/s0006-2952(99)00283-x [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1999 Dec 15;58(12):1881-9. doi: 10.1016/s0006-2952(99)00283-x.