Asset Details
Do you wish to reserve the book?
Neural peptidase endothelin-converting enzyme 1 regulates endothelin 1–induced pruritus
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Neural peptidase endothelin-converting enzyme 1 regulates endothelin 1–induced pruritus
Do you wish to request the book?
Neural peptidase endothelin-converting enzyme 1 regulates endothelin 1–induced pruritus
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Neural peptidase endothelin-converting enzyme 1 regulates endothelin 1–induced pruritus
2014
Overview
In humans, pruritus (itch) is a common but poorly understood symptom in numerous skin and systemic diseases. Endothelin 1 (ET-1) evokes histamine-independent pruritus in mammals through activation of its cognate G protein-coupled receptor endothelin A receptor (ETAR). Here, we have identified neural endothelin-converting enzyme 1 (ECE-1) as a key regulator of ET-1-induced pruritus and neural signaling of itch. We show here that ETAR, ET-1, and ECE-1 are expressed and colocalize in murine dorsal root ganglia (DRG) neurons and human skin nerves. In murine DRG neurons, ET-1 induced internalization of ETAR within ECE-1-containing endosomes. ECE-1 inhibition slowed ETAR recycling yet prolonged ET-1-induced activation of ERK1/2, but not p38. In a murine itch model, ET-1-induced scratching behavior was substantially augmented by pharmacological ECE-1 inhibition and abrogated by treatment with an ERK1/2 inhibitor. Using iontophoresis, we demonstrated that ET-1 is a potent, partially histamine-independent pruritogen in humans. Immunohistochemical evaluation of skin from prurigo nodularis patients confirmed an upregulation of the ET-1/ETAR/ECE-1/ERK1/2 axis in patients with chronic itch. Together, our data identify the neural peptidase ECE-1 as a negative regulator of itch on sensory nerves by directly regulating ET-1-induced pruritus in humans and mice. Furthermore, these results implicate the ET-1/ECE-1/ERK1/2 pathway as a therapeutic target to treat pruritus in humans.
Publisher
American Society for Clinical Investigation
Subject
/ Age
/ Animals
/ Aspartic Acid Endopeptidases - antagonists & inhibitors
/ Aspartic Acid Endopeptidases - genetics
/ Aspartic Acid Endopeptidases - metabolism
/ Cellular signal transduction
/ Endothelin-1 - administration & dosage
/ Endothelin-Converting Enzymes
/ Enzymes
/ Female
/ Ganglia, Spinal - metabolism
/ Humans
/ Kinases
/ Male
/ Metalloendopeptidases - antagonists & inhibitors
/ Metalloendopeptidases - genetics
/ Metalloendopeptidases - metabolism
/ Mice
/ Neurons
/ Pain
/ Pruritus
/ Receptor, Endothelin A - metabolism
/ Software
