Function Of Novel Analgesic Peptides From The Tree Frog Of Hyla Japonica

There are many bioactive compounds in amphibian skin secretions, these compounds can be used to against environmental harmful factors. There are four types of habitats for anurans including aquatic (e.g., genus of Xenopus), semiterrestrial (e.g., genus of Rana), terrestrial (e.g., genus of Bufo), and arboreal (e.g., genus of Hyla) environments. Most of Hyla amphibians are tree-adapted species and live in vegetation near water bodies in forest and in open areas. In these environments, they may encounter many biotic and abiotic risk factors, such as preys, microorganisms and radiations. Their green or brown skins may facilitate their living in forest canopy. In addition, chemical array in tree frog skins also plays important roles for maintaining their survival. In this study, two novel analgesic peptides (analgesin-HJ, FWPVI-NH2 and analgesin-HJ(I5T), FWPVT-NH2) were first identified from the skin of the tree frog, Hyla japonica, and their molecular weight are 659.84 Da and 647.78 Da, respectively. There are 171 amino acid residues in the precursor encoding analgesin-HJs. The precursor contains 10 copies of mature peptide, which include 9 copies of analgesin-HJ and one copy of analgesin-HJ(I5T). Results from analgesic experiments using mice models including abdominal writhing induced by acetic acid, formalin-induced paw licking, and thermal pain test indicated that this two peptides exerted comparable analgesic activities with morphine. Analgesic function of analgesin-HJ in the model of carrageenan-induced edema also supports this hypothesis. In addition, they had ability to inhibit inflammatory factor secretion induced by lipopolysaccharides (LPS). In the preliminary research on the analgesic mechanism of analgesin-HJ, we found that analgesin HJ has no obvious opioid receptor agonist activity. The analgesia mechanism remains to be further in-depth study. Considering their easy production, storage, transfer and potential analgesic activity, analgesin-HJs might be exciting leading compounds or templates for the development of novel analgesic agent.