Description:
<p> Organic lead and tin compounds stimulate an increase of free arachidonic acid (AA) in HL-60 cells. This fatty acid is involved in numerous health problems and physiological mechanisms. Three major pathways result in a liberation of AA from membrane phospholipids and there is evidence that G-proteins serve as couplers within all three pathways. Therefore we investigated the influence of pertussis toxin (PT) on the organometallic-induced AA liberation. The effect of all studied compounds (organotin and organo-lead) was diminished by PT. We conclude that the organometals activate PLA<sub>2</sub>to some extent via a PT-sensitive pathway. The ionophor A 23187 (1-10 μM) led to an increase of free AA by raising the intracellular Ca<sup>2+</sup>level. One of the postulated ways of AA release is via Ca<sup>2+</sup>channel activation; phospholipases are Ca<sup>2+</sup>dependent. Thus, we examined the necessity of free intracellular Ca<sup>2+</sup>for the organometallic effect. The Ca<sup>2+</sup>chelator EGTA inhibited the increase of free AA induced by organometals. This is true also for verapamil, a Ca<sup>2+</sup>channel blocker. Quinacrine, which is thought to be an inhibitor of phospholipase A<sub>2</sub>( PLA<sub>2</sub>), prevented the AA liberation from membrane phospholipids induced by organometals. This could be due to the inhibition of PLA<sub>2</sub>, but it could also be the result of an inhibited Ca<sup>2+</sup>influx. </p>