title: Oxytocin induced a biphasic increase in the intracellular Ca2+ concentration of porcine myometrial cells: participation of a pertussis toxin-insensitive G-protein, inositol 1,4,5-trisphosphate-sensitive Ca2+ pool, and Ca2+ channels.
abstract: This study investigated the underlying mechanisms of oxytocin (OT)-induced increases in intracellular Ca2+ concentrations ([Ca2+]i) in acutely dispersed myometrial cells from prepartum sows. A dose-dependent increase in [Ca2+]i was induced by OT (0.1 nM to 1 microM) in the presence and absence of extracellular Ca2+ ([Ca2+]e). [Ca2+]i was elevated by OT in a biphasic pattern, with a spike followed by a sustained plateau in the presence of [Ca2+]e. However, in the absence of [Ca2+]e, the [Ca2+]i response to OT became monophasic with a lower amplitude and no plateau, and this monophasic increase was abolished by pretreatment with ionomycin, a Ca2+ ionophore. Administration of OT (1 microM) for 15 sec increased inositol 1,4,5-trisphosphate (IP3) formation by 61%. Pretreatment with pertussis toxin (PTX, 1 microgram/ml) for 2 hr failed to alter the OT-induced increase in [Ca2+]i and IP3 formation. U-73122 (30 nM to 3 microM), a phospholipase C (PLC) inhibitor, depressed the rise in [Ca2+]i by OT dose dependently. U-73122 (3 microM) also abolished the OT-induced IP3 formation. Thapsigargin (2 microM), an inhibitor of Ca(2+)-ATPase in the endoplasmic reticulum, did not increase [Ca2+]i. However, it did time-dependently inhibit the OT-induced increase in [Ca2+]i. Nimodipine (1 microM), a voltage-dependent Ca2+ channel (VDCC) blocker, inhibited the OT-induced plateau by 26%. La3+ (1 mM), a nonspecific Ca2+ channel blocker, abrogated the OT-induced plateau. In whole-cell patch-clamp studies used to evaluate VDCC activities, OT (0.1 microM) increased Ca2+ current (ICa) by 40% with no apparent changes in the current-voltage relationship.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames 50011, USA.
authors.forename: R
authors.initials: R
authors.lastname: Zhuge
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: T H
authors.initials: TH
authors.lastname: Chen
authors.forename: W H
authors.initials: WH
authors.lastname: Hsu
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D009215:Myometrium / Q000378:metabolism*; D010121:Oxytocin / Q000494:pharmacology*; D037342:Pertussis Toxin; D015398:Signal Transduction; D013552:Swine; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D007295:Inositol Phosphates; D010566:Virulence Factors, Bordetella; D010121:Oxytocin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium