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Am J Physiol Endocrinol Metab 276: E345-E351, 1999;
0193-1849/99 $5.00
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Vol. 276, Issue 2, E345-E351, February 1999

Oxytocin increases the [Ca2+]i sensitivity of human myometrium during the falling phase of phasic contractions

Keena McKillen1,2, Steven Thornton3, and Colin W. Taylor1

1 Department of Pharmacology, University of Cambridge, Cambridge CB2 1QJ; 2 Department of Obstetrics and Gynaecology, University of Cambridge, Rosie Hospital, Cambridge CB2 2SW; and 3 Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom

Oxytocin is commonly used to induce or augment labor, but its mode of action is uncertain. To address the issue, isometric tension and the intracellular free Ca2+ concentration ([Ca2+]i) were simultaneously recorded from isolated strips of pregnant human myometrium loaded with fura 2. The changes in [Ca2+]i and tension during phasic contractions were indistinguishable in myometrium taken before or after the onset of labor, enabling samples to be pooled. Oxytocin (10 nM) had no effect on basal [Ca2+]i or tension, but it increased both the [Ca2+]i and the tension recorded during phasic contractions. Analysis of the [Ca2+]i-tension relationship revealed that during the falling (relaxation) phase of the contractile response, oxytocin increased the tension recorded at each [Ca2+]i. By manipulating extracellular Ca2+ during phasic contractions, it was possible to ensure that the [Ca2+]i signals were similar in the presence and absence of oxytocin, yet oxytocin still improved the [Ca2+]i-tension relationship. We conclude that 10 nM oxytocin increases the [Ca2+]i sensitivity of the contractile proteins only after a contraction has begun, possibly by causing inhibition of myosin light chain phosphatase.

smooth muscle; signal transduction; labor; pregnancy; uterus


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