Effects of Mn2+ on the responses induced by different spasmogens in the oestrogen-primed rat uterus.
We investigated the effect of Mn2+ 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 Ca2+-free, Mn2+ (0.54 mM)-containing solution, high K+ or low Na+ solutions produced contractions of smaller amplitude than those observed in a normal Ca2+ (0.54 mM) solution, which were abolished by nifedipine (1 microM). Oxytocin (1 microM) and neurokinin A (1 microM, in the presence of phosphoramidon 1 microM) evoked nifedipine-insensitive contractile responses similar to (oxytocin) or smaller (neurokinin A) in amplitude than those observed in Ca2+ (0.54 mM)-containing solution. In strips loaded with Ca2+ (2.16 mM) for 10 min and then exposed to a Ca2+- and Mn2+-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 microM). When preparations were loaded with Mn2+ (2.16 mM) for 10 min, only the small, tonic contraction was observed. In Ca2+-containing solution, Mn2+ (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. Mn2+ 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, Mn2+ acts as an antagonist of Ca2+ influx through L-type voltage-operated Ca2+ channels. In addition, Mn2+ enters the cell mainly through nifedipine-insensitive receptor-operated channels and, to a lesser degree, through L-type Ca2+ channels to produce contraction by directly activating the contractile machinery.
Magraner
J
J
Instituto de Investigaciones Científicas Isla de La Cartuja, Institutode Química, Sevilla, Spain.
Morcillo
E
E
Ausina
P
P
Pinto
F M
FM
Martín
J D
JD
Moreau
J
J
Anselmi
E
E
Barrachina
M D
MD
Cortijo
J
J
Advenier
C
C
Candenas
M L
ML
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004558:Electric Stimulation; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis; D008345:Manganese / Q000494:pharmacology*; D015288:Neurokinin A / Q000494:pharmacology*; D010121:Oxytocin / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*
D004967:Estrogens; D007295:Inositol Phosphates; D008345:Manganese; D010121:Oxytocin; D015288:Neurokinin A; D012964:Sodium; D011188:Potassium; D002118:Calcium