Review Article

Phoenixin: a novel brain-gut-skin peptide with multiple bioactivity

Rong-Ming L YU1, Alan COWAN2,3, Ying ZHANG3, Yi-Hung CHEN4, Siok L DUN3, Jaw-Kang CHANG1, Nae J DUN3, Jin Jun LUO3,5
1 Phoenix Pharmaceuticals Inc, Burlingame, CA 94010, USA
2 Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
3 Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
4 Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan, China
5 Department of Neurology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
Correspondence to: Jin Jun LUO:,
DOI: 10.1038/aps.2017.195
Received: 17 October 2017
Accepted: 8 December 2017
Advance online: 15 March 2018


In this brief review we summarize the current fndings relative to the discovery of a small peptide ligand, phoenixin (PNX). Using a bioinformatic approach, two novel peptides PNX-14 and PNX-20 containing 14 and 20 amino acids, respectively, were isolated from diverse tissues including the brain, heart, lung and stomach. Mass spectrometry analysis identified a major and minor peak corresponding to PNX-14 and PNX-20, in rat or mouse spinal cord extracts. With the use of a rabbit polyclonal antiserum, phoenixin immunoreactivity (irPNX) was detected in discrete areas of the rodent brain including several hypothalamic subnuclei and dorsal motor nucleus of the vagus. In addition, irPNX was detected in a population of sensory ganglion cells including dorsal root ganglion, nodose ganglion and trigeminal ganglion, and in cell processes densely distributed to the superficial layers of the dorsal horn, nucleus of the solitary tract and spinal trigeminal tract. irPNX cell processes were also detected in the skin and myenteric plexus, suggesting a braingut and/or brain-skin connection. Pharmacological studies show that PNX-14 injected subcutaneously to the nape of the neck of mice provoked dose-dependent repetitive scratching bouts directed to the back of the neck with the hindpaws. Our result suggests that the peptide PNX-14 and/or PNX-20, may serve as one of the endogenous signal molecules transducing itch sensation. Additionally, results from other laboratories show that exogenous PNX may affect a number of diverse behaviors such as memory formation, depression, reproduction, food-intake and anxiolytic-like behaviors.
Keywords: neuropeptide; brain-gut-skin peptide; phoenixin; dorsal motor nucleus of the vagus; dorsal root ganglion; hypothalamus; myenteric plexus; nodose ganglion; itch sensation

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