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  • Title: The effect of maternal ketanserin treatment on foetal 5-HT receptor function in umbilical cord artery of pre-eclamptic patients.
    Author: Hanff LM, Gupta S, MaassenVanDenBrink A, Steegers EA, Saxena PR, Vulto AG, Visser W.
    Journal: Neonatology; 2007; 92(4):240-7. PubMed ID: 17556842.
    Abstract:
    BACKGROUND: Maternal treatment with the 5-HT(2A) receptor antagonist ketanserin (KT) in pre-eclamptic patients is associated with a high placental transmission of KT, resulting in pharmacologically active levels of KT in the umbilical cord artery (UCA) and the neonate. Prolonged exposure to a 5-HT receptor antagonist may influence the functionality of foetal 5-HT receptors and compromise foetal development. OBJECTIVE: To study whether exposure to KT influences the characteristics of foetal 5-HT receptors, functional studies were performed on 5-HT(2A) and 5-HT(1B/1D) receptors in UCA from pre-eclamptic patients treated with KT. METHODS: UCAs were obtained, immediately after delivery, from pre-eclamptic patients (n = 7), treated antenatally with intravenous KT. Pre-eclamptic patients (n = 13), not treated with KT (non-KT), were included as a control group. Segments of UCA were prepared and mounted in tissue baths and isometric force changes were determined. Cumulative concentration response curves to 5-HT and to the 5-HT(1B/1D )receptor agonist sumatriptan were constructed in the absence or presence of the 5-HT(2A) receptor antagonist KT or the 5-HT(1B/1D) receptor antagonist GR125743, respectively. RESULTS: All UCA segments showed contractile responses to both 5-HT and sumatriptan, and the concentration response curves showed a rightward shift with increasing concentrations of KT and GR125743, respectively, indicating the presence of functional 5-HT(2A) and 5-HT(1B/1D) receptors in the foetal tissue. No significant differences were found in maximum response (E(max))(expressed in percent of response on 100 mM KCl) or potency (pEC(50)) of 5-HT in both groups (E(max) = 141 +/- 7.7%, pEC(50) = 7.67 +/- 0.26 in KT-treated group and E(max) = 162 +/- 12.6%, pEC(50) = 7.69 +/- 0.14 in non-KT treated group, respectively). No significant differences were found in the potency of the antagonist KT in both study groups (pK(b) = 7.65 +/- 0.31 in KT group and 7.46 +/- 0.17 in non-KT group, respectively). Similarly, with sumatriptan, no significant differences were found between KT-treated patients and non-KT treated patients (E(max) = 142 +/- 16.2 and 140 +/- 14.7%, respectively, pEC(50) = 6.17 +/- 0.37 and 6.41 +/- 0.28 respectively, pK(b) of GR125743 = 7.83 +/- 0.48 and 8.43 +/- 0.29, respectively). CONCLUSION: Foetal exposure to KT in pre-eclamptic patients does not seem to influence the functional characteristics of 5-HT(2A) and 5-HT(1B/1D) receptors in the UCA.
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