Neurokinin B and pre-eclampsia: a decade of discovery

Abstract

At the start of the last decade, we provided evidence that levels of the peptide neurokinin B were highly elevated in pre-eclampsia. We hypothesized that elevated levels of neurokinin B may be an indicator of pre-eclampsia and that treatment with certain neurokinin receptor antagonists may be useful in alleviating the symptoms. At the time of the original hypothesis many questions remained outstanding. These included - Does neurokinin B have any diagnostic value in the detection and diagnosis of pre-eclampsia? - What is the cause of the elevated levels of neurokinin B during pre-eclampsia? - What is the physiological significance of neurokinin B in the placenta? This review discusses the answers to these questions taking into account the subsequent developments of the past ten years and analyzing the plethora of discoveries that have arisen from those initial observations.

Neurokinin 3 Receptor and Phosphocholine Transferase

“…PCYT1b). 16, 17 Posttranslational modification (PTM) is an essential biological mechanism to control fundamental cellular and systemic functions. Modifications of biological molecules typically serve to amplify or diminish activity of the molecule, or alter their ligand-receptor relationship.…”

“…18 One of the endogenous phosphocholinated molecules is NKB and phosphocholine modified NKB (PC-NKB) preferentially activates neurokinin 3 receptor (NK3R), a Gq coupled transmembrane receptor. 16, 17 The NK3R has been hypothesized to be instrumental in the development of hypertension in pregnancy, however, due to the pleiotropic nature of NKB, the exact mechanism of specific activation of the NK3R has not been elucidated. In view of the facts that 1) NKB is produced predominantly from placentas and contributes to PE by activating NK3R, 2) NKB is phosphocholinated, 3) placenta is one of two tissues expressing PCT, and 4) CRP is elevated in PE and known to bind with phosphocholine, we hypothesize that elevated CRP is not just an early biomarker but likely a pathogenic factor contributing to PE by binding to phosphocholinated NKB and preferentially activating NK3R.…”

Placental lesions associated with maternal underperfusion are more frequent in early-onset than in late-onset preeclampsia

“…This specific pregnancy disorder can be the result of multiple mechanisms of disease [9,10,13,16,20,21,25,32–36,42,43,46,47,53,56,57,59,64–66,70,78,80–82,84,87,88,91,102,105,111,112,116,120,123,129,134,136,144,154], is adaptive in nature [2,15,44,96,97,113,135] and has a long subclinical phase [19,22,63,67,68,98,100,122, 125,140,145]. Due to its syndromic nature, several attempts have been made to classify patients with PE into distinct subgroups in order to improve un derstanding of its pathophysiology [148–150,153], predict maternal/fetal complications [4,27,89,124,126] and to develop individualized preventive or therapeutic interventions [11,23,128,138].…”

Hepatic portal vein flow and three dimensional indices of hepatic perfusion in pre-eclampsia compared with normal pregnancy

“…Among the many proposed aetiologies of pre-eclampsia, one that is particularly interesting is that by Page et al (2000;Page 2010). In these papers, the authors propose that in preeclampsia, Neurokinin B is secreted by the placenta, which causes venoconstriction of the portal veins.…”

“…In these papers, the authors propose that in preeclampsia, Neurokinin B is secreted by the placenta, which causes venoconstriction of the portal veins. Th is in turn, impairs liver function and results in the release of a circulating factor (Page 2010;Page et al 2000). Th is circulating factor then causes endothelial damage and results in arterial constriction manifested by reduced organ perfusion and hypertension (Page et al 2000).…”