PT - JOURNAL ARTICLE AU - Jeehyeon Bae AU - Marc Peters-Golden AU - Rita Loch-Caruso TI - Stimulation of Pregnant Rat Uterine Contraction by the Polychlorinated Biphenyl (PCB) Mixture Aroclor 1242 May Be Mediated by Arachidonic Acid Release through Activation of Phospholipase A<sub>2</sub> Enzymes DP - 1999 May 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 1112--1120 VI - 289 IP - 2 4099 - http://jpet.aspetjournals.org/content/289/2/1112.short 4100 - http://jpet.aspetjournals.org/content/289/2/1112.full SO - J Pharmacol Exp Ther1999 May 01; 289 AB - The polychlorinated biphenyl (PCB) mixture Aroclor 1242 (A1242) increases frequency of contractions of pregnant rat uteri, suggesting a possible mechanism for decreased gestational age and increased spontaneous abortion in women and animals exposed to PCBs. In the present study, we hypothesized that A1242-induced stimulation of uterine contraction is mediated by arachidonic acid released by phospholipase A2 (PLA2) enzymes. Isometric uterine contraction was measured in longitudinal uterine strips isolated from gestation day 10 rat. Pretreatment of uterine strips with the PLA2 inhibitor (E)-6-(bromomethylene)tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one (HELSS) or manoalide, or an inhibitor of the G protein of PLA2, isotetrandrine, completely prevented the increase of contractile frequency induced by 50 μM A1242. However, the phospholipase C inhibitors 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (NCDC) and neomycin were unable to block stimulation of uterine contraction by A1242. In accordance, A1242 (100 μM) did not release inositol phosphates from myo-[3H]inositol-labeled myometrial cells, whereas myometrial cells prelabeled with [3H]arachidonic acid released arachidonic acid in a concentration- and time-dependent manner after exposure to A1242 (10–100 μM). A1242 significantly stimulated arachidonic acid release in the absence of extracellular calcium, although the release was attenuated. Analysis of the eicosanoids released by A1242 indicated that only 0.83% of released [3H]arachidonic acid was metabolized to eicosanoids and 99.07% remained as free arachidonate. Uterine contraction increased in strips exposed to exogenous arachidonic acid (1–100 μM). This study suggests that A1242 stimulates contraction in pregnant rat uterus by a mechanism involving PLA2-mediated arachidonic acid release, and that arachidonic acid, rather than eicosanoids, may mediate A1242 uterotonic action in the uterus. The American Society for Pharmacology and Experimental Therapeutics