Lindane-induced inhibition of spontaneous contractions of pregnant rat uterus

Hexachlorocyclohexanes (HCHs) are prevalent insecticides. Lindane (gamma-HC H) inhibits uterine gap junctions but beta-HCH does not. Because gap juncti ons promote coordination of oscillatory uterine contractions, we hypothesiz ed that lindane, but not beta-HCH, would inhibit uterine contractions. Uter ine strips from midgestation rats were suspended in standard muscle baths a nd exposed to HCHs in a cumulative manner. Lindane induced concentration-de pendent decreases in contraction force (ED50 of 9.2 mu M) and complete uter ine quiescence at 30 mu M. In contrast, beta-HCH had no effect on contracti on force, but 20 to 200 mu M beta-HCH increased contraction frequency in a concentration-dependent manner. Isomer-specific differences in uterine resp onses were observed at similar HCH isomer tissue concentrations. Additional ly, the phospholipase A(2) inhibitor and antioxidant quinacrine increased t he ED50 for contraction force inhibition to 84.5 mu M lindane. Lindane also increased cAMP concentrations. Lindane and beta-HCH have distinctly differ ent actions in the uterus. Lindane's inhibitory action may involve cAMP, ar achidonic acid, or oxidative stress. (C) 1999 Elsevier Science Inc. All rig hts reserved.