title: Effect of indometacin pretreatment on protamine sulfate-mediated relaxation of the isolated rat uterus: the role of the antioxidative defense system.
abstract: Previous results in this laboratory indicate that protamine sulfate (PS) evokes dose-dependent relaxation of both spontaneous and calcium ion-induced uterus activity mediated predominantly by potassium channels and, to a small extent, via β-adrenergic receptors or nitric oxide (NO)-dependent pathways. Indometacin is a nonselective inhibitor of cyclooxygenase (COX 1 and COX 2) that has the ability to delay premature labor by reducing uterine contractions through the inhibition of prostanglandin synthesis in the uterus. This study investigates the effects of indometacin (0.1 and 1 μg/ml) pretreatment on the PS-induced relaxation of isolated uterine smooth muscle. Indometacin pretreatment per se did not change the activity of the uteri. However, indometacin significantly increased PS-induced relaxation of spontaneous uterine contractions. Indometacin pretreatment significantly decreased the magnitude and slope of PS-induced relaxation of calcium ion-induced uterine contractions. Indometacin pretreatment increased CuZnSOD activity and slightly increased GR activity during spontaneous uterine contractions when compared to PS alone. In calcium ion-induced contractions, indometacin pretreatment increased CuZnSOD, GSH-Px and GR activities. These results suggest that, in addition to its COX inhibitory effects, indometacin influences the effects of PS. Therefore, it is possible that indometacin regulates diverse cell functions via its association with lipid membranes by altering micro-environments within the membranes. The above-mentioned processes appear to be partly mediated by redox processes involving ROS, lipid peroxides and antioxidant enzymes. The extent of the PS-mediated effect as different in spontaneous versus calcium ion-induced active uteri.
authors: High Medical School Milutin Milanković, Belgrade, Serbia.
authors: Jelena
authors: J
authors: Kordić-Bojinović
authors: Zorana
authors: Z
authors: Oreščanin-Dušić
authors: Marija
authors: M
authors: Slavić
authors: Ratko
authors: R
authors: Radojičić
authors: Mihajlo
authors: M
authors: Spasić
authors: Slobodan R
authors: SR
authors: Milovanović
authors: Duško
authors: D
authors: Blagojević
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D011479:Protamines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D016861:Cyclooxygenase Inhibitors; D011479:Protamines; D013482:Superoxide Dismutase; D002118:Calcium; D007213:Indomethacin