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This Article Full Text Full Text (PDF) All Versions of this Article: 581/1/91    most recent jphysiol.2007.129726v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Minosyan, T. Y. Articles by Stefani, E. Search for Related Content PubMed PubMed Citation Articles by Minosyan, T. Y. Articles by Stefani, E. Related Collections Cellular

¹ Department of Anaesthesiology, Division of Molecular Medicine
² Department of Molecular & Medical Pharmacology
³ Department of Physiology
⁴ Brain Research Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095-1778, USA

The 5-hydroxytryptamine (5-HT) type 2 receptor family is involved in multiple physiological functions in smooth muscle including proliferation, differentiation and contraction. In myometrium, 5-HT₂ receptors not only play a role in contraction but also regulate the activity of hypertrophic genes during pregnancy. Here we investigated whether 5-HT_2A receptors were up-regulated during gestation and whether changes in expression could be correlated with changes in 5-HT-induced contractions in late pregnant myometrium. 5-HT tension dose–response curves showed that 5-HT-induced myometrial contractility is drastically increased in late pregnancy when compared to non-pregnant conditions. The 5-HT maximum tension (% of 80 mM KCl contracture) increased from 17 ± 2% in non-pregnant to 54 ± 7% in late pregnant myometrium. This tension increase took place without significant changes in the 5-HT sensitivity as EC₅₀ values were similar in non-pregnant and late pregnant myometrium (0.11 ± 0.03 µM and 0.17 ± 0.02 µM, respectively). The increased 5-HT-induced contraction at the end of pregnancy was associated with up-regulation of 5-HT_2A transcript (5-fold) and protein (6-fold) levels. These functional and biochemical studies provide evidence that myometrium remodelling during pregnancy is in part associated with up-regulation of 5-HT_2A transcript and protein levels resulting in higher 5-HT-induced contractile responses. We conclude that the higher 5-HT-induced contractile response results from a higher density of 5-HT_2A receptors having the same properties as in non-pregnant myometrium.

(Received 1 February 2007; accepted after revision 21 March 2007; first published online 29 March 2007)
Corresponding author E. Stefani: David Geffen School of Medicine at UCLA, Department of Anaesthesiology, BH-520A CHS Box 957115, Los Angeles, CA 90095-7115, USA. Email: estefani{at}ucla.edu

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