Participation of Ca2+/calmodulin during activation of rat neutrophils by polychlorinated biphenyls.
The effects of Ca2+ and Ca2+/calmodulin on the polychlorinated biphenyl (PCB)-induced activation of phospholipase A2 (PLA2) in rat neutrophils were examined. The commercial PCB mixture Aroclor 1242 induced activation of PLA2 and promoted an increase in the intracellular free calcium concentration ([Ca2+]i). Bromoenol lactone (BEL), an inhibitor of the Ca2+-independent PLA2 isoform (iPLA2) activated by PCBs, did not abrogate the increase in [Ca2+]i, suggesting that this change in Ca2+ concentration is not downstream from the activation of iPLA2. TMB-8 [8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate], a blocker of the release of intracellular Ca2+, decreased Aroclor 1242-induced stimulation of PLA2 with a maximal inhibition of 17% at 50 microM. These two results suggest little direct dependence between the PCB-induced activation of iPLA2 and increase in [Ca2+]i. Calmidazolium and W7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide], two chemically distinct calmodulin inhibitors, inhibited Aroclor 1242-induced PLA2 activity, whereas trifluoperazine (TFP), another inhibitor of calmodulin, had no effect at noncytotoxic concentrations. Thus, activation of PLA2 is dependent, in part, on calmodulin. Furthermore, both TFP and Aroclor 1242 inhibited neutrophil degranulation stimulated by the bacterial peptide formyl-methionyl-leucyl-phenylalanine. These results raise the possibility that some of the effects of PCBs on neutrophil function can be explained by effects on Ca2+/calmodulin-dependent processes.
Olivero
J
J
Department of Pharmacology and Toxicology, National Food Safety and Toxicology Center and Institute for Environmental Toxicology, Michigan State University, East Lansing, MI 48824, USA.
Ganey
P E
PE
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004785:Environmental Pollutants / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects* / Q000502:physiology; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014268:Trifluoperazine / Q000494:pharmacology
D001140:Aroclors; D002147:Calmodulin; D018492:Dopamine Antagonists; D004785:Environmental Pollutants; D014268:Trifluoperazine; C027423:aroclor 1242; D011078:Polychlorinated Biphenyls; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium