Phoenixin: A candidate pruritogen in the mouse

Abstract

Phoenixin (PNX) is a 14-amino acid amidated peptide (PNX-14) or an N-terminal extended 20-residue amidated peptide (PNX-20) recently identified in neural and non-neural tissue. Mass spectrometry analysis identified a major peak corresponding to PNX-14, with negligible PNX-20, in mouse spinal cord extracts. Using a previously characterized antiserum that recognized both PNX-14 and PNX-20, PNX-immunoreactivity (irPNX) was detected in a population of dorsal root ganglion (DRG) cells and in cell processes densely distributed to the superficial layers of the dorsal horn; irPNX cell processes were also detected in the skin. The retrograde tracer, Fluorogold, injected subcutaneously (s.c.) to the back of the cervical and thoracic spinal cord of mice, labeled a population of DRG, some of which were also irPNX. PNX-14 (2, 4 and 8 mg/kg) injected s.c.to the nape of the neck provoked dose-dependent repetitive scratching bouts directed to the back of the neck with the hindpaws. The number of scratching bouts varied from 16–95 in 30 min, commencing within 5 min post-injection and lasted 10–15 min. Pretreatment of mice at −20 min with nalfurafine (20 µg/kg, s.c.), the kappa opioid receptor agonist, significantly reduced the number of bouts induced by PNX-14 (4 mg/kg) compared with that of saline-pretreated mice. Our results suggest that the peptide, PNX-14, serves as one of the endogenous signal molecules transducing itch sensation in the mouse.

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

“…Third, phoenixin-induced scratching is attenuated by nalfurafine, the kappa opioid receptor agonist, which is a known agent effective against excessive scratching caused by several chemically diverse pruritogens [20] . Collectively, the results support the contention that phoenixin is one of the signaling molecules involved in bidirectional transfer of itch sensation in the mouse [12] .…”

“…Insofar as a biological role of phoenixin in the peripheral nervous system is concerned, several observations are consistent with the suggestion that the peptide may engage in transmitting itch sensation from the skin to the spinal cord or brainstem [12] . First, phoenixin is expressed in DRGs with their cell processes projecting centrally to the dorsal horn and peripherally to the skin, providing the neurochemical substrate for the transfer of sensory signals.…”

“…It is of interest to note that irPNX nerve fibers are detected underneath the skin of rodents. Further, subcutaneous injections of the retrograde fluorescent tracer Fluorogold labeled a population of DRG cells, some of which also contain irPNX, raising the possibility that the peptide released underneath the skin may act on sensory nerve fibers, transmitting sensory signal from the skin to the spinal cord [12] .…”

“…An abundance of phoenixin in the central and peripheral nervous systems suggests that the peptide may serve as a signaling molecule targeting multiple sites [8,12,13,14] . Because of a Exogenous PNX-14 acting on gonadotrophins was found to increase gonadotropin releasing hormone (GnRH) receptor expression and GnRH secretion, which in turn, enhanced the release of luteinizing hormone [8] .…”

Phoenixin-20 Stimulates mRNAs Encoding Hypothalamo-Pituitary-Gonadal Hormones, is Pro-Vitellogenic, and Promotes Oocyte Maturation in Zebrafish

“…roles, PNX-20 is a potent regulator of behavioral response as well 6,[17][18][19] . Upregulation of kiss 1 post-PNX-20 administration suggests in addition to the reproductive regulatory role, PNX might be involved in the regulation of behavior in teleost.…”