Effects of benzo-a-pyrene on oxytocin-induced Ca2+ oscillations in myometrial cells.
Benzo-a-pyrene (BaP) is a polycyclic aromatic hydrocarbon that exists as a major environmental pollutant. The effect of this carcinogen/mutagen upon myometrial Ca(2+) signaling in a human myometrial cell line (PHM1) was examined. Exposure of cells to BaP did not alter basal Ca(2+) levels or the inositol(1,4,5) trisphosphate-releasable Ca(2+) pool. However, BaP significantly decreased the initial oxytocin-induced Ca(2+) transient and the frequency of oxytocin-induced Ca(2+)oscillations as well as delayed their onset. To determine the specific effects of BaP, pharmacologic agents that target intracellular Ca(2+) homeostasis mechanisms were used. Genistein (a non-specific tyrosine kinase inhibitor) and AG1478 (an epidermal growth factor receptor blocker) markedly reduced the oxytocin-induced Ca(2+) oscillations in control, but had no effect in BaP treated cells. Addition of epidermal growth factor or serum before or after oxytocin restored the Ca(2+) oscillations in BaP treated cells to a level similar to control cells, while the K(+) channel blocker tetraethylammonium chloride, partially restored the Ca(2+) response. These data suggest that the tyrosine kinase pathway, which is part of the G-protein coupled receptor pathway response to oxytocin in PHM1 cells, is a target of BaP action and that EGF or serum can restore the oxytocin-induced Ca(2+) oscillations.
Depatrment of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843-4458, USA. rmouneimne@cvm.tamu.edu
Rola
R
Barhoumi
Igbal
I
Awooda
Youssef
Y
Mouneimne
Stephen
S
Safe
Robert C
RC
Burghardt
D000328:Adult; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010121:Oxytocin / Q000494:pharmacology*; D011247:Pregnancy; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines; D019789:Tetraethylammonium / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology
D002274:Carcinogens, Environmental; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; D001564:Benzo(a)pyrene; D010121:Oxytocin; D004815:Epidermal Growth Factor; D019789:Tetraethylammonium; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D002118:Calcium