A. Kafer et Hf. Krug, EFFECTS OF ORGANOMETALS ON CELLULAR SIGNALING .1. INFLUENCE OF METABOLIC-INHIBITORS ON METAL-INDUCED ARACHIDONIC-ACID LIBERATION, Environmental health perspectives, 102, 1994, pp. 325-330
Organic lead and tin compounds stimulate an increase of free arachidon
ic acid (AA) in HL-60 cells. This fatty acid is involved in numerous h
ealth problems and physiological mechanisms. Three major pathways resu
lt in a liberation of AA from membrane phospholipids and there is evid
ence that G-proteins serve as couplers within ail three pathways. Ther
efore we investigated the influence of pertussis toxin (PT) on the org
anometallic-induced AA liberation. The effect of all studied compounds
(organotin and organo-lead) was diminished by PT. We conclude that th
e organometals activate PLA(2) to some extent via a PT-sensitive pathw
ay. The ionophor A 23187 (1-10 mu M) led to an increase of free AA by
raising the intracellular Ca2+ level. One of the postulated ways of AA
release is via Ca2+ channel activation; phospholipases are Ca2+ depen
dent. Thus, we examined the necessity of free intracellular Ca2+ for t
he organometallic effect. The Ca2+ chelator EGTA inhibited the increas
e of free AA induced by organometals. This is true also for verapamil,
a Ca2+ channel blocker. Quinacrine, which is thought to be an inhibit
or of phospholipase A(2)(PLA(2)), prevented the AA liberation from mem
brane phospholipids induced by organometals. This could be due to the
inhibition of PLA(2), but it could also be the result of an inhibited
Ca2+ influx.