Excessive placental secretion of neurokinin B during the third trimester causes pre-eclampsia

N. M. Page, R. J. Woods, S. M. Gardiner, K. Lomthaisong, R. T. Gladwell, D. J. Butlin, I. T. Manyonda and P. J. Lowry ()
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N. M. Page: School of Animal and Microbial Sciences, The University of Reading
R. J. Woods: School of Animal and Microbial Sciences, The University of Reading
S. M. Gardiner: School of Biomedical Sciences, The University of Nottingham
K. Lomthaisong: School of Animal and Microbial Sciences, The University of Reading
R. T. Gladwell: School of Animal and Microbial Sciences, The University of Reading
D. J. Butlin: School of Animal and Microbial Sciences, The University of Reading
I. T. Manyonda: Department of Obstetrics and Gynaecology St George's Hospital
P. J. Lowry: School of Animal and Microbial Sciences, The University of Reading

Nature, 2000, vol. 405, issue 6788, 797-800

Abstract: Abstract Pre-eclampsia is a principal cause of maternal morbidity and mortality, affecting 5–10% of first pregnancies worldwide. Manifestations include increased blood pressure, proteinuria, coagulopathy and peripheral and cerebral oedema. Although the aetiology and pathogenesis remain to be elucidated, the placenta is undoubtedly involved, as termination of pregnancy eradicates the disease. Here we have cloned a complementary DNA from human placental messenger RNA encoding a precursor protein of 121 amino acids which gives rise to a mature peptide identical to the neuropeptide neurokinin B (NKB)1 of other mammalian species. In female rats, concentrations of NKB several-fold above that of an animal 20 days into pregnancy caused substantial pressor activity. In human pregnancy, the expression of NKB was confined to the outer syncytiotrophoblast of the placenta, significant concentrations of NKB could be detected in plasma as early as week 9, and plasma concentrations of NKB were grossly elevated in pregnancy-induced hypertension and pre-eclampsia. We conclude that elevated levels of NKB in early pregnancy may be an indicator of hypertension and pre-eclampsia, and that treatment with certain neurokinin receptor antagonists may be useful in alleviating the symptoms.

Date: 2000
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DOI: 10.1038/35015579

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