Inhibition of the liberation of arachidonic acid by cadmium ions in rabbit alveolar macrophages.
The effects of CdCl2 on the liberation of arachidonic acid (20:4) from membrane phospholipids of A23187-stimulated rabbit alveolar macrophages and on the activity of phospholipase A2 (PLA2) in a cytosolic fraction were studied. Alveolar macrophages were prelabeled with [3H]arachidonic acid (20:4) and then treated with A23187. This treatment resulted in a remarkable increase in the liberation of [3H]20:4 from their phospholipids. Exposure of cells to Cd2+ inhibited the liberation of [3H]20:4 in a dose-dependent manner. Liberation of [3H]20:4 from cell lipids was calcium dependent and the inhibitory effect of Cd2+ competed with the stimulatory effect of Ca2+. When Ca2+ was removed from the incubation medium, Cd2+ did not influence the liberation of [3H]20:4. Entry of 45Ca2+ into cells was enhanced by treatment of A23187. However, Cd2+ did not influence the cellular uptake of 45Ca2+. Treatment with A23187 markedly enhanced entry of 109Cd2+ into cells. The effect of Cd2+ on the activity of phospholipase A2 was determined with 1-palmitoyl-2-[14C]arachidonoyl-sn-glycero-3-phosphocholine as substrate. Calcium-dependent activation of PLA2 was observed and Cd2+ inhibited activation in a dose-dependent manner. These results suggest that exposure of alveolar macrophages to Cd2+ causes a reduction in the rate of liberation of 20:4 from cell lipids, as a possible result of the inhibition of PLA2 activity by Cd2+.
Kudo
N
N
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Nakagawa
Y
Y
Waku
K
K
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002104:Cadmium / Q000378:metabolism / Q000494:pharmacology*; D002106:Cadmium Radioisotopes; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002132:Calcium Radioisotopes; D002474:Cell-Free System / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D066298:In Vitro Techniques; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D011817:Rabbits
D002106:Cadmium Radioisotopes; D002132:Calcium Radioisotopes; D010713:Phosphatidylcholines; D010743:Phospholipids; D002104:Cadmium; D016718:Arachidonic Acid; D000001:Calcimycin; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium