Hemokinins

Introduction

In 2000, the discovery of a fourth mammalian tachykinin in the mouse that was named hemokinin-1 (HK-1) has enabled the realization of a completely new and diverse group of novel tachykinins and tachykinin gene-related peptides in the mammals. Some hemokinins were studied later, which include hemokinin-1 (HK-1) in mouse and rat, human HK-1 (hHK-1) and hHK (4-11) in humans. Hemokinin is another member of the tachykinin family.

Mechanism of action

HK-1 has the differences in ligand binding at the NK2 and NK3 receptors, which may be attributed to by the highly divergent N-terminal sequences of these peptides, or the significantly species-dependent variability in the homologies of the NK2 and NK3 receptors as compared with the highly species conserved NK1 receptor. Because its primary target population also expresses high levels of the Pptc gene product that encodes the precursor protein of the HK-1, peptide HK-1 is likely to act either as a paracrine or autocrine factor.

Application of Hemokinins

Study has investigated the binding affinity and agonist efficacy of the hemokinin peptides at each of the three-mammalian tachykinin receptors. The results of the experiment showed that HK-1 has equipotent affinity to substance P (SP) at the human tachykinin NK1 receptor. In contrast, HK-1 displays an ~ 3.8 times lower affinity than SP at the human tachykinin NK3 receptor and there is an ~2.8 times greater affinity for HK-1 at the human tachykinin NK2 receptor than SP. In bioassays, the capacity of HK-1 to induce plasma extravasation and to promote mast cell degranulation has been found to be same as that of SP. Therefore, the behavior of HK-1 and SP in producing hypotension and salivary secretion in guinea pigs was almost superimposable, which suggested that HK-1 is an equipotent NK1 receptor agonist in vivo. And some activities previously attributed to SP, such as the modulation of immune responses, may actually be mediated by HK-1 in physiological conditions. Besides, HK-1 is another important regulator of the growth of B cell precursors at the pro-B-pre-B stage.

References

1. Zhang, Y., Lu, L., Furlonger, C., Wu, G. E., & Paige, C. J. (2000). Hemokinin is a hematopoietic-specific tachykinin that regulates B lymphopoiesis. Nature immunology, 1(5), 392.
2. Page, N. M. (2004). Hemokinins and endokinins. Cellular and Molecular Life Sciences CMLS, 61(13), 1652-1663.
3. Borbély, é., Hajna, Z., Nabi, L., Scheich, B., Tékus, V., László, K., ... & Lénárd, L. (2017). Hemokinin-1 mediates anxiolytic and anti-depressant-like actions in mice. Brain, behavior, and immunity, 59, 219-232.