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Molecular Pain

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Open Access 01-12-2015 | Research

Protein kinase Cδ mediates histamine-evoked itch and responses in pruriceptors

Authors: Manouela V Valtcheva, Steve Davidson, Chengshui Zhao, Michael Leitges, Robert W Gereau IV

Published in: Molecular Pain | Issue 1/2015

Abstract

Background

Itch-producing compounds stimulate receptors expressed on small diameter fibers that innervate the skin. Many of the currently known pruritogen receptors are G_q Protein-Coupled Receptors (G_qPCR), which activate Protein Kinase C (PKC). Specific isoforms of PKC have been previously shown to perform selective functions; however, the roles of PKC isoforms in regulating itch remain unclear. In this study, we investigated the novel PKC isoform PKCδ as an intracellular modulator of itch signaling in response to histamine and the non-histaminergic pruritogens chloroquine and β-alanine.

Results

Behavioral experiments indicate that PKCδ knock-out (KO) mice have a 40% reduction in histamine-induced scratching when compared to their wild type littermates. On the other hand, there were no differences between the two groups in scratching induced by the MRGPR agonists chloroquine or β-alanine. PKCδ was present in small diameter dorsal root ganglion (DRG) neurons. Of PKCδ-expressing neurons, 55% also stained for the non-peptidergic marker IB4, while a smaller percentage (15%) expressed the peptidergic marker CGRP. Twenty-nine percent of PKCδ-expressing neurons also expressed TRPV1. Calcium imaging studies of acutely dissociated DRG neurons from PKCδ-KO mice show a 40% reduction in the total number of neurons responsive to histamine. In contrast, there was no difference in the number of capsaicin-responsive neurons between KO and WT animals. Acute pharmacological inhibition of PKCδ with an isoform-specific peptide inhibitor (δV1-1) also significantly reduced the number of histamine-responsive sensory neurons.

Conclusions

Our findings indicate that PKCδ plays a role in mediating histamine-induced itch, but may be dispensable for chloroquine- and β-alanine-induced itch.

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Title: Protein kinase Cδ mediates histamine-evoked itch and responses in pruriceptors
Authors: Manouela V Valtcheva
Steve Davidson
Chengshui Zhao
Michael Leitges
Robert W Gereau IV
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2015
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/1744-8069-11-1

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Protein kinase Cδ mediates histamine-evoked itch and responses in pruriceptors

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Results

Conclusions

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