| First Author | Munanairi A | Year | 2018 |
| Journal | Cell Rep | Volume | 23 |
| Issue | 3 | Pages | 866-877 |
| PubMed ID | 29669290 | Mgi Jnum | J:264867 |
| Mgi Id | MGI:6198944 | Doi | 10.1016/j.celrep.2018.03.087 |
| Citation | Munanairi A, et al. (2018) Non-canonical Opioid Signaling Inhibits Itch Transmission in the Spinal Cord of Mice. Cell Rep 23(3):866-877 |
| abstractText | Chronic itch or pruritus is a debilitating disorder that is refractory to conventional anti-histamine treatment. Kappa opioid receptor (KOR) agonists have been used to treat chronic itch, but the underlying mechanism remains elusive. Here, we find that KOR and gastrin-releasing peptide receptor (GRPR) overlap in the spinal cord, and KOR activation attenuated GRPR-mediated histamine-independent acute and chronic itch in mice. Notably, canonical KOR-mediated Galphai signaling is not required for desensitizing GRPR function. In vivo and in vitro studies suggest that KOR activation results in the translocation of Ca(2+)-independent protein kinase C (PKC)delta from the cytosol to the plasma membrane, which in turn phosphorylates and inhibits GRPR activity. A blockade of phospholipase C (PLC) in HEK293 cells prevented KOR-agonist-induced PKCdelta translocation and GRPR phosphorylation, suggesting a role of PLC signaling in KOR-mediated GRPR desensitization. These data suggest that a KOR-PLC-PKCdelta-GRPR signaling pathway in the spinal cord may underlie KOR-agonists-induced anti-pruritus therapies. |
