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.
Minosyan
Tamara Y
TY
Department of Anaesthesiology, David Geffen School of Medicine at UCLA, BH-520A CHS Box 957115, Los Angeles, CA 90095-7115, USA.
Lu
Rong
R
Eghbali
Mansoureh
M
Toro
Ligia
L
Stefani
Enrico
E
D000818:Animals; D005260:Female; D009119:Muscle Contraction / Q000502:physiology*; D009215:Myometrium / Q000502:physiology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D012701:Serotonin / Q000502:physiology*; D015854:Up-Regulation
D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D012701:Serotonin