PMID- 8894168
OWN - NLM
STAT- MEDLINE
DCOM- 19970206
LR  - 20190512
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 119
IP  - 3
DP  - 1996 Oct
TI  - Inhibition by fenamates of calcium influx and proliferation of human lymphocytes.
PG  - 487-94
AB  - 1. Flufenamic and tolfenamic acids have recently been shown to inhibit 
      receptor-mediated calcium influx in human neutrophils. The present work was 
      designed to study the effects of these two nonsteroidal anti-inflammatory drugs 
      on human peripheral blood lymphocyte activation. 2. Peripheral blood mononuclear 
      cells (PBMNCs; containing 90% lymphocytes) were stimulated by mitogen 
      concanavalin A (Con A) or by a combination of an inhibitor of microsomal 
      Ca(2+)-adenosine triphosphatase thapsigargin (TG) and phorbol myristate acetate 
      (PMA). The effects of the two fenamates on cell proliferation were compared with 
      respective changes in calcium metabolism. 3. Flufenamic and tolfenamic acids 
      (10-100 microM) inhibited both Con A and TG + PMA-induced [3H]-thymidine 
      incorporation in a dose-dependent manner. At the same concentration range, the 
      two fenamates inhibited the increase in intracellular free calcium concentration 
      induced by Con A or TG + PMA. This effect was due to inhibition of calcium influx 
      whereas calcium release from intracellular stores remained unaltered. 4. The 
      inhibition of divalent cation influx was confirmed by showing that fenamates 
      inhibited TG + PMA-induced Mn2+ influx. 5. The inhibitory effects of fenamates on 
      PBMNC proliferation and Ca2+ influx were qualitatively similar with those of SK&F 
      96365, an earlier known inhibitor of receptor-mediated calcium entry. Ketoprofen, 
      a chemically different prostaglandin synthetase inhibitor did not show similar 
      suppressive effects on PBMNCs. 6. The data suggest that flufenamic and tolfenamic 
      acids suppress proliferation of human peripheral blood lymphocytes by a mechanism 
      which involves inhibition of Ca2+ influx and is not related to inhibition of 
      prostanoid synthesis.
FAU - Kankaanranta, H
AU  - Kankaanranta H
AD  - Medical School, University of Tampere, Finland.
FAU - Luomala, M
AU  - Luomala M
FAU - Kosonen, O
AU  - Kosonen O
FAU - Moilanen, E
AU  - Moilanen E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (ortho-Aminobenzoates)
RN  - 11028-71-0 (Concanavalin A)
RN  - 3G943U18KM (tolfenamic acid)
RN  - 42Z2K6ZL8P (Manganese)
RN  - 60GCX7Y6BH (Flufenamic Acid)
RN  - 67526-95-8 (Thapsigargin)
RN  - I61V87164A (1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Analysis of Variance
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Calcium/*metabolism
MH  - Cell Division/drug effects
MH  - Concanavalin A/antagonists & inhibitors
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/*pharmacology
MH  - Flufenamic Acid/*pharmacology
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Lymphocytes/*drug effects/physiology
MH  - Manganese/metabolism
MH  - Tetradecanoylphorbol Acetate/*antagonists & inhibitors
MH  - Thapsigargin/*antagonists & inhibitors
MH  - ortho-Aminobenzoates/*pharmacology
PMC - PMC1915711
EDAT- 1996/10/01 00:00
MHDA- 1996/10/01 00:01
PMCR- 1997/10/01
CRDT- 1996/10/01 00:00
PHST- 1996/10/01 00:00 [pubmed]
PHST- 1996/10/01 00:01 [medline]
PHST- 1996/10/01 00:00 [entrez]
PHST- 1997/10/01 00:00 [pmc-release]
AID - 10.1111/j.1476-5381.1996.tb15698.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 1996 Oct;119(3):487-94. doi: 10.1111/j.1476-5381.1996.tb15698.x.