The effect of maternal ketanserin treatment on foetal 5-HT receptor function in umbilical cord artery of pre-eclamptic patients.
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).


CONCLUSIONS
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.
Hanff
L M
LM
Department of Hospital Pharmacy, Erasmus University Medical Centre, Rotterdam, The Netherlands. l.hanff@erasmusmc.nl
Gupta
S
S
MaassenVanDenBrink
A
A
Steegers
E A P
EA
Saxena
P R
PR
Vulto
A G
AG
Visser
W
W
D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides / Q000494:pharmacology; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007650:Ketanserin / Q000494:pharmacology / Q000627:therapeutic use*; D011225:Pre-Eclampsia / Q000188:drug therapy* / Q000503:physiopathology; D011247:Pregnancy; D011725:Pyridines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D018170:Sumatriptan / Q000494:pharmacology; D014469:Umbilical Arteries / Q000187:drug effects / Q000502:physiology*
D000959:Antihypertensive Agents; D001549:Benzamides; C107225:N-(4-methoxy-3-(4-methylpiperazin-1-yl)phenyl)-3-methyl-4-(4-pyridyl)benzamide; D011725:Pyridines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D018170:Sumatriptan; D007650:Ketanserin