Lindane-induced inhibition of spontaneous contractions of pregnant rat uterus.
Hexachlorocyclohexanes (HCHs) are prevalent insecticides. Lindane (gamma-HCH) inhibits uterine gap junctions but beta-HCH does not. Because gap junctions promote coordination of oscillatory uterine contractions, we hypothesized that lindane, but not beta-HCH, would inhibit uterine contractions. Uterine strips from midgestation rats were suspended in standard muscle baths and exposed to HCHs in a cumulative manner. Lindane induced concentration-dependent decreases in contraction force (ED50 of 9.2 microM) and complete uterine quiescence at 30 microM. In contrast, beta-HCH had no effect on contraction force, but 20 to 200 microM beta-HCH increased contraction frequency in a concentration-dependent manner. Isomer-specific differences in uterine responses were observed at similar HCH isomer tissue concentrations. Additionally, the phospholipase A2 inhibitor and antioxidant quinacrine increased the ED50 for contraction force inhibition to 84.5 microM lindane. Lindane also increased cAMP concentrations. Lindane and beta-HCH have distinctly different actions in the uterus. Lindane's inhibitory action may involve cAMP, arachidonic acid, or oxidative stress.
Criswell
K A
KA
Department of Environmental Health Sciences, School of Public Health II, University of Michigan, Ann Arbor 48109-2029, USA.
Loch-Caruso
R
R
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D001556:Hexachlorocyclohexane / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000633:toxicity*; D066298:In Vitro Techniques; D007306:Insecticides / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000633:toxicity*; D009126:Muscle Relaxation / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism; D010852:Picrotoxin / Q000494:pharmacology; D011247:Pregnancy; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
D000242:Cyclic AMP; D001556:Hexachlorocyclohexane; D007306:Insecticides; D010852:Picrotoxin; D011796:Quinacrine; C023888:beta-hexachlorocyclohexane