Endocrine Abstracts (2001) 2 OC24

THE ACTIVATION OF PERIPHERAL NEUROKININ RECEPTORS IN THE PATHOLOGY OF PRE-ECLAMPSIA

NJ Bell, GJ Graham, JM Gibbins, PJ Lowry & NM Page


School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, Berks, RG6 6AJ.


Mild symptoms of pre-eclampsia (PE) include hypertension and proteinuria, but more severe cases develop cerebrovascular accident, liver capsule distention, platelet pathology, pulmonary oedema and renal failure. As we have recently reported neurokinin B (NKB) levels to be significantly raised in the plasma of women with PE, the aim of this study is to establish the pathological role of NKB in this disease.

NKB acts predominantly through the NK3 receptor, but at high concentrations will activate NK2 and NK1 receptors.The peripheral expression sites of each neurokinin receptor were mapped from a cDNA panel of 25 human tissues using semi-quantitative RT-PCR. Amplified PCR products were visualized after gel electrophoresis, column purified, cloned and sequenced. Specific NK3 receptor expression was revealed in 10 tissues, including the brain, kidney, placenta, uterus, lung, adrenal gland, skeletal muscle, and platelets, tissues commonly affected in PE. NK1 and NK2 receptors were found in all tissues supporting a potential role for high circulating NKB levels in the systemic pathology observed in more serious cases.

NKR expression was also studied in the human placenta in the first and third trimester to understand their normal physiological roles in the utero-placental complex. Preliminary results indicate all three NK receptors are present in the placenta and uterus. Placental NKR expression appears to increase during trophoblast invasion (in which defects are a key early factor for the development of PE) at week 13 but then decrease at term.

Whilst placental NKB increases to term, preliminary observations show placental neutral endopeptidase (NEP) is high at weeks 9-13 but absent at term so may now allow NKB to activate peripheral receptors. Hence, NK, NEP and receptor expression are fully supportive of a significant role for NKB in the pathology of PE and could provide a target for treatment of this multi-system disorder of pregnancy.

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