6533b7d9fe1ef96bd126c321

RESEARCH PRODUCT

Effects of Mn2+ on the responses induced by different spasmogens in the oestrogen-primed rat uterus

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Abstract We investigated the effect of Mn 2+ on the mechanical responses evoked by high K + (60 mM) or low Na + (25 mM) solutions, oxytocin and neurokinin A in the oestrogen-primed rat uterus. In a Ca 2+ -free, Mn 2+ (0.54 mM)-containing solution, high K + or low Na + solutions produced contractions of smaller amplitude than those observed in a normal Ca 2+ (0.54 mM) solution, which were abolished by nifedipine (1 μM). Oxytocin (1 μM) and neurokinin A (1 μM, in the presence of phosphoramidon 1 μM) evoked nifedipine-insensitive contractile responses similar to (oxytocin) or smaller (neurokinin A) in amplitude than those observed in Ca 2+ (0.54 mM)-containing solution. In strips loaded with Ca 2+ (2.16 mM) for 10 min and then exposed to a Ca 2+ - and Mn 2+ -free, EGTA (3 mM)-containing medium for 4 min, both oxytocin and neurokinin A induced transient contraction followed by a small sustained response. The transient component of the response was abolished by cyclopiazonic acid (10 μM). When preparations were loaded with Mn 2+ (2.16 mM) for 10 min, only the small, tonic contraction was observed. In Ca 2+ -containing solution, Mn 2+ (0.01–10 mM) inhibited in a concentration-dependent manner the rhythmic contractions developed either spontaneously or by electrical stimulation as well as high K + - and neurokinin A-induced contractions. Mn 2+ also abolished the rhythmic, but not the tonic component of the response to oxytocin, and the preparation remained maximally contracted. These data suggest that in the oestrogen-primed rat uterus, Mn 2+ acts as an antagonist of Ca 2+ influx through L-type voltage-operated Ca 2+ channels. In addition, Mn 2+ enters the cell mainly through nifedipine-insensitive receptor-operated channels and, to a lesser degree, through L-type Ca 2+ channels to produce contraction by directly activating the contractile machinery.