Neurokinin B has been traditionally regarded as a neuropeptide being confined to the CNS, with no peripheral expression. This situation was the cause of some confusion as its preferred receptor (NK3R) is found mainly on peripheral organs such as the portal vein, mesenteric vessels and the heart with relatively low levels in the brain. In 2000 our laboratory reported the placenta to be an abundant peripheral endocrine source of NKB, giving rise to significant plasma concentrations suggesting that NK3 receptor containing tissues were responsible for pregnancy induced hypertension. In the present study we have re-investigated the possible presence of NKB in peripheral tissues in the non-pregnant state. Although previous reports had failed to detect immunoreactive NKB outside the placenta, real-time quantitative PCR has revealed significant expression of the NKB pre-cursor gene in numerous peripheral tissues. Using our original radioimmunoasay, significant NKB-like immuno-reactivity was detected in rat thymus, testes and brain as well as in placenta and pregnant rat plasma. However, a highly specific two site ELISA, which recognises both the N- and C-termini of NKB only detected peptide in rat brain, with undetectable amounts in any of the peripheral tissues tested (including the placenta), reminiscent of the earlier study. After gel filtration immunoreactive NKB extracted from rat brain was detected by both assays and eluted in the expected position of the synthetic 10mer standard whereas the material in extracts of rat placenta and thymus was detected only by the radioimmunoassay and was found in both cases to elute slightly earlier than the brain form. These observations suggest that a differentially processed form of NKB is found in some peripheral tissues, it may be the preferred ligand at the peripheral NKB receptor (NK3R) and that care should be exercised when interpreting results using assays specific for the brain form.
22 - 24 Mar 2004
British Endocrine Societies