Characterization of the endokinins: Human tachykinins with cardiovascular activity

Page, N. M., Bell, N. J., Gardiner, S. M., Manyonda, I. T., Brayley, K. J., Strange, P. G. and Lowry, P. J. (2003) Characterization of the endokinins: Human tachykinins with cardiovascular activity. Proceedings of the National Academy of Sciences of the United States of America, 100 (10). pp. 6245-6250. ISSN 0027-8424

Abstract/Summary

We report four human tachykinins, endokinins A, B, C, and D (EKA-D), encoded from a single tachykinin precursor 4 gene that generates four mRNAs (alpha, beta, gamma, and delta). Tachykinin 4 gene expression was detected primarily in adrenal gland and in the placenta, where, like neurokinin B, significant amounts of EKB-like immunoreactivity were detected. EKA/B 10-mers displayed equivalent affinity for the three tachykinin receptors as substance P (SP), whereas a 32-mer N-terminal extended form of EKB was significantly more potent than EKA/B or SP. EKC/D, which possess a previously uncharacterized tachykinin motif, FQGLL-NH2, displayed low potency, EKA/B displayed identical hemodynamic effects to SP in rats, causing short-lived falls in mean arterial blood pressure associated with tachycardia, mesenteric vasoconstriction, and marked hindquarter vasodilatation. Thus, EKA/B could be the endocrine/paracrine agonists at peripheral SP receptors and there may be as yet an unidentified receptor(s) for EKC/D.