Increased 5-HT contractile response in late pregnant rat myometrium is associated with a higher density of 5-HT2A receptors.

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-HT2A 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 microM and 0.17 +/- 0.02 microM, respectively). The increased 5-HT-induced contraction at the end of pregnancy was associated with up-regulation of 5-HT2A transcript (approximately 5-fold) and protein (approximately 6-fold) levels. These functional and biochemical studies provide evidence that myometrium remodelling during pregnancy is in part associated with up-regulation of 5-HT2A 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-HT2A receptors having the same properties as in non-pregnant myometrium.