Acute inhibition of spontaneous uterine contractions by an estrogenic polychlorinated biphenyl is associated with disruption of gap junctional communication.
An estrogenic polychlorinated biphenyl, 4-hydroxy-2',4', 6'-trichlorobiphenyl (4-OH-TCB), inhibits oscillatory uterine contractions immediately. Because increased gap junction formation is associated with the development of synchronized uterine contractions at term, we examined whether the inhibitory effect of 4-OH-TCB on spontaneous oscillatory contractions was due to the disruption of gap junctional communication. The effect of 4-OH-TCB on gap junctional communication was determined by intercellular Lucifer yellow dye transfer in primary cultures of myometrial myocytes isolated from midgestation rats. Intercellular dye transfer was inhibited by 4-OH-TCB or 17beta-estradiol in a concentration-dependent manner. The inhibitory effect of 4-OH-TCB on intercellular dye transfer was reversed by tetraethylammonium (TEA). To examine effects on uterine contraction, longitudinal uterine strips were excised from midgestation rats and placed in muscle baths for isometric force measurement. Spontaneous uterine oscillation was suppressed by 4-OH-TCB or 17beta-estradiol. The inhibitory effects of 4-OH-TCB and 17beta-estradiol on spontaneous oscillations were counteracted by TEA but were not affected by a calcium ionophore (A23187) or a calcium-dependent potassium channel blocker (apamin). These results suggest that the acute inhibition of spontaneous oscillatory contractions by an estrogenic polychlorinated biphenyl may result from the disruption of intercellular communication.
Department of Environmental and Industrial Health, University of Michigan, Ann Arbor, Michigan 48109, USA.
M L
ML
Tsai
K
K
Cesen-Cummings
R C
RC
Webb
R
R
Loch-Caruso
D000818:Animals; D015153:Blotting, Western; D000001:Calcimycin / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D018031:Connexin 43 / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D019850:Heptanol / Q000494:pharmacology; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects* / Q000502:physiology; D014599:Uterus / Q000166:cytology / Q000187:drug effects / Q000502:physiology
D018031:Connexin 43; C105195:4-hydroxy-2',4',6'-trichlorobiphenyl; D000001:Calcimycin; D004958:Estradiol; D019789:Tetraethylammonium; D019850:Heptanol; D011078:Polychlorinated Biphenyls