PMID- 2898031
OWN - NLM
STAT- MEDLINE
DCOM- 19880725
LR  - 20190725
IS  - 0021-5198 (Print)
IS  - 0021-5198 (Linking)
VI  - 46
IP  - 3
DP  - 1988 Mar
TI  - Effects of various drugs on superoxide generation, arachidonic acid release and 
      phospholipase A2 in polymorphonuclear leukocytes.
PG  - 275-84
AB  - The effects of variety of drugs on metabolic burst and phospholipase A2 in 
      polymorphonuclear leukocytes (PMNs) were investigated. The stimulation of PMNs by 
      n-formyl-methionyl-leucyl-phenylalanine (FMLP) causes arachidonic acid (AA) to be 
      released in the cells concomitantly with the generation of superoxide anion. 
      These variables were effectively diminished with some clinically employed drugs 
      including chlorpromazine, trifluoperazine, azelastine, clemastine and mepacrine 
      at the lower concentration of 20 microM. In contrast, indomethacin and procaine 
      were ineffective even at the higher concentration of 100 microM. Subcellular 
      fractionation of PMNs revealed that phospholipase A2 activity was located both in 
      the plasma membrane-rich fraction as well as the granule-microsome-rich fraction, 
      and the potency of inhibition of membrane-bound phospholipase A2 by the above 
      mentioned drugs was: indomethacin (IC50 = 3 microM) less than chlorpromazine less 
      than azelastine and clemastine (IC50 greater than 100 microM). The low potency of 
      antipsychotropic drugs and antihistaminic drugs in inhibiting the fractionated 
      phospholipase A2 contrast with the high efficiency with which they inhibit the 
      superoxide generation and the AA release from stimulated PMNs. The AA releases 
      from the PMNs stimulated by FMLP or calcium ionophore (A23187) were almost 
      equally diminished by various drugs at the lower concentration. From these 
      observations, it appeared likely that these drugs might inhibit the metabolic 
      stimulations of PMNs at the sites of the Ca2+-dependent activation processes of 
      the enzymes responsible for the AA release and the superoxide generation.
FAU - Taniguchi, K
AU  - Taniguchi K
AD  - Department of Toxicology, Niigata College of Pharmacy, Japan.
FAU - Urakami, M
AU  - Urakami M
FAU - Takanaka, K
AU  - Takanaka K
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Jpn J Pharmacol
JT  - Japanese journal of pharmacology
JID - 2983305R
RN  - 0 (Arachidonic Acids)
RN  - 0 (Histamine H1 Antagonists)
RN  - 0 (Phthalazines)
RN  - 11062-77-4 (Superoxides)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 37H9VM9WZL (Calcimycin)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - EC 3.1.- (Phospholipases)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.4 (Phospholipases A2)
RN  - U42B7VYA4P (Chlorpromazine)
RN  - XXE1CET956 (Indomethacin)
RN  - ZQI909440X (azelastine)
SB  - IM
MH  - Animals
MH  - Arachidonic Acid
MH  - Arachidonic Acids/*metabolism
MH  - Calcimycin/pharmacology
MH  - Chlorpromazine/pharmacology
MH  - Histamine H1 Antagonists/pharmacology
MH  - In Vitro Techniques
MH  - Indomethacin/pharmacology
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/drug effects/*enzymology/metabolism
MH  - Phospholipases/*metabolism
MH  - Phospholipases A/*metabolism
MH  - Phospholipases A2
MH  - Phthalazines/pharmacology
MH  - Rabbits
MH  - Superoxides/*metabolism
EDAT- 1988/03/01 00:00
MHDA- 1988/03/01 00:01
CRDT- 1988/03/01 00:00
PHST- 1988/03/01 00:00 [pubmed]
PHST- 1988/03/01 00:01 [medline]
PHST- 1988/03/01 00:00 [entrez]
AID - 10.1254/jjp.46.275 [doi]
PST - ppublish
SO  - Jpn J Pharmacol. 1988 Mar;46(3):275-84. doi: 10.1254/jjp.46.275.