Phorbol 12-myristate, 13-acetate potentiates the action of the calcium ionophore in stimulating arachidonic acid release and production of phosphatidic acid in rabbit neutrophils.
The addition of the tumor-promoting phorbol 12-myristate, 13-acetate to rabbit neutrophils greatly potentiates the effect of the calcium ionophore A23187 on [3H]-arachidonic acid release and [32P]-phosphatidic acid generation. At 5 X 10(-8) M A23187, the addition of 20 ng/ml PMA potentiates the action of the ionophore on [3H]-arachidonic acid release by 5-fold. At 5 X 10(-7) M A23187, PMA enhances [32P]-phosphatidic acid production by 1.5-fold. Incubation of the neutrophils with 5 X 10(-7) M ionophore for two minutes causes a significant increase in the [32P] phosphatidic acid production but does not affect the levels of [32P]-phosphatidylinositol or [32P]-phosphatidylinositol 4,5 bis-phosphate. In addition, increasing the sodium chloride concentrations in the suspending medium causes an increase in the level of phosphatidylinositol 4,5 bis-phosphate. These results suggest that the phorbol ester either acting directly or through the activation of protein kinase C modulates significantly the activities of the various forms of phospholipases, particularly A2, and/or increases the availability or amounts of their substrates.
Volpi
M
M
Molski
T F
TF
Naccache
P H
PH
Feinstein
M B
MB
Sha'afi
R I
RI
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology*; D004357:Drug Synergism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010704:Phorbols / Q000494:pharmacology*; D010712:Phosphatidic Acids / Q000096:biosynthesis*; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism; D011817:Rabbits; D012965:Sodium Chloride / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D001095:Arachidonic Acids; D010704:Phorbols; D010712:Phosphatidic Acids; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C037178:phosphatidylinositol 4-phosphate; D016718:Arachidonic Acid; D000001:Calcimycin; D012965:Sodium Chloride; D013755:Tetradecanoylphorbol Acetate