PMID- 2242033
OWN - NLM
STAT- MEDLINE
DCOM- 19901210
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 40
IP  - 9
DP  - 1990 Nov 1
TI  - Stimulation of human polymorphonuclear leukocytes potentiates the uptake of 
      diclofenac and the inhibition of chemotaxis.
PG  - 2039-45
AB  - Diclofenac sodium, a non-steroidal anti-inflammatory drug, has been shown to 
      impair the stimulation of human polymorphonuclear leukocytes (PMNs) by 
      chemoattractants. To gain insight into the mechanism of action of this agent, we 
      investigated the uptake of diclofenac by resting and activated PMNs and the 
      effect of the drug on PMN locomotion. During incubation of resting PMNs at 37 
      degrees in the presence of 78 microM (25 micrograms/mL) diclofenac, drug uptake 
      reached a plateau in less than 2 min. The resulting cellular to extracellular 
      diclofenac concentration ratio (C/E) was 1.01 +/- 0.13 (mean +/- SD). Stimulation 
      of PMNs at 37 degrees but not at 4 degrees with the chemoattractant 
      formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate (PMA), 
      induced a rise in diclofenac uptake, which was dependent on incubation time and 
      diclofenac and stimulus concentrations. Maximal C/E was 1.83 +/- 0.18 and 4.40 
      +/- 0.60 (mean +/- SD) for PMNs stimulated with 10 microM fMLP and 0.16 microM 
      PMA, respectively. The diclofenac associated with PMNs was predominantly present 
      in the soluble fraction of disrupted cells. Interestingly, PMNs which were 
      pretreated with diclofenac and stimulated with fMLP, exhibited impaired random 
      and directional locomotion induced by activated serum, as compared to controls, 
      i.e. PMNs treated with diclofenac alone or fMLP alone. Thus, stimulation of PMNs 
      enhances diclofenac uptake and potentiates the drug impairment of chemotactic 
      activity. These findings could explain, in part, the observed anti-inflammatory 
      properties of this compound.
FAU - Perianin, A
AU  - Perianin A
AD  - Departement de Pharmacologie, CNRS URA 595, Hopital Cochin-Port Royal, Paris, 
      France.
FAU - Giroud, J P
AU  - Giroud JP
FAU - Hakim, J
AU  - Hakim J
LA  - eng
PT  - Journal Article
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 144O8QL0L1 (Diclofenac)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Cells, Cultured
MH  - Chemotaxis, Leukocyte/*drug effects
MH  - Diclofenac/*pharmacokinetics/pharmacology
MH  - Humans
MH  - N-Formylmethionine Leucyl-Phenylalanine/*pharmacology
MH  - Neutrophils/*drug effects/metabolism
MH  - Stimulation, Chemical
MH  - Tetradecanoylphorbol Acetate/*pharmacology
EDAT- 1990/11/01 00:00
MHDA- 1990/11/01 00:01
CRDT- 1990/11/01 00:00
PHST- 1990/11/01 00:00 [pubmed]
PHST- 1990/11/01 00:01 [medline]
PHST- 1990/11/01 00:00 [entrez]
AID - 0006-2952(90)90234-C [pii]
AID - 10.1016/0006-2952(90)90234-c [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1990 Nov 1;40(9):2039-45. doi: 10.1016/0006-2952(90)90234-c.