Role of hemokinin-1 in health and disease.

Hemokinin-1 (HK-1), the newest tachykinin encoded by the Tac4 gene was discovered in 2000. Its name differs from that of the other members of this peptide family due to its first demonstration in B lymphocytes. Since tachykinins are classically found in the nervous system, the significant expression of HK-1 in blood cells is a unique feature of this peptide. Due to its widespread distribution in the whole body, HK-1 is involved in different physiological and pathophysiological functions involving pain inflammation modulation, immune regulation, respiratory and endocrine functions, as well as tumor genesis. Furthermore, despite the great structural and immunological similarities to substance P (SP), the functions of HK-1 are often different or the opposite. They both have the highest affinity to the tachykinin NK1 receptor, but HK-1 is likely to have a distinct binding site and signalling pathways. Moreover, several actions of HK-1 different from SP have been suggested to be mediated via a presently not identified own receptor/target molecule. Therefore, it is very important to explore its effects at different levels and compare its characteristics with SP to get a deeper insight in the different cellular mechanisms. Since HK-1 has recently been in the focus of intensive research, in the present review we summarize the few clinical data and experimental results regarding HK-1 expression and function in different model systems obtained throughout the 16years of its history. Synthesizing these findings help to understand the complexity of HK-1 actions and determine its biomarker values and/or drug development potentials.