Endocrine Abstracts

Of the many neuropeptide hormones that are secreted by the placenta our attention focussed some years ago on the tachykinin, neurokinin B (NKB) as the blood concentration of this decapeptide was found to be raised in pre-eclampsia and nearly all of the life threatening symptoms seen in this disease appeared to be through progressive activation of the three neurokinin receptors. Interestingly only a limited number of antisera raised against the synthetic 10mer (the form found in neural tissue) cross reacted fully with placental NKB despite clear evidence for expression of its mRNA and proteolytic processing of its peptide precursor in this tissue. Further characterisation of placental NKB revealed that placental NKB eluted on gel filtration in the approximate position of a 13mer and this was confirmed by TOF mass spectrometry of the purified material which gave a mass of 1580. Although this mass is consistent with dimethylated NKB-Gly-Lys-Arg, further characterisation (immunological and mass spectrometric fragment analysis) suggested a novel post-translational modification containing phosphocholine (PC) with some evidence for glycerol and a coordinated alkene. The structure that fits all the data is that a form of platelet activating factor (PAF) is attached via the glycerol 2 position to the aspartyl side chain at position 4 of NKB and thus now implicates placental NKB it in the platelet pathology seen in pre-eclampsia. As it has been reported that it is the PC group per se attached to certain proteins secreted by filarial nematodes imparts them with immune inhibitory properties and thus survival in the host over long periods, attaching PC to placental secretory peptide hormones (it can also be found on the placental precursors of CRF, ACTH and activin) may result in a similar effect on the mother’s immune system in allowing the survival of the feto-placental unit and may be responsible for other changes seen in pregnancy such as remission from rheumatoid arthritis and asthma.

Note: Due to a technical fault this abstract does not appear in the printed version.