Blockade of epidermal growth factor-induced uterine contractions by indomethacin or nordihydroguaritic acid.
Epidermal growth factor (EGF) induces uterine contractions in an in vitro system. As an initial approach to elucidating the cellular mechanism for this action of EGF, we have characterized this effect pharmacologically in uteri from castrate, estrogenprimed mature rats. EGF-induced contractions are observed in both intact tissue and isolated myometrium, are dependent on extracellular calcium and are inhibited by nifedipine and chlorpromazine. Both indomethacin and nordihydroguaritic acid (NGA) inhibit EGF-induced uterine contractions. At the maximum doses which do not affect contractile responses to prostaglandin E2 or carbachol, indomethacin (10 microM) alone or NGA (1 microM) alone only decrease the effect of EGF by 60 to 80%, but indomethacin and NGA in combination abolish totally the response to the growth factor. Arachidonic acid also causes uterine contractions in this system. EGF increases uterine contractions in the presence of a submaximal (1 microM) but not a maximal (10 microM) dose of arachidonic acid. These findings suggest that EGF-induced contractions result from a mobilization of myometrial arachidonic acid, production of intermediates via both lipoxygenase and cyclooxygenase catalyzed pathways and a resultant influx of extracellular calcium.
Gardner
R M
RM
Department of Biology, Villanova University, Pennsylvania.
Stancel
G M
GM
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors; D009637:Masoprocol / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects*
D001095:Arachidonic Acids; D002396:Catechols; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D004815:Epidermal Growth Factor; D009637:Masoprocol; D009543:Nifedipine; D002118:Calcium; D002746:Chlorpromazine; D007213:Indomethacin