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Capsaicin up-regulates protease-activated receptor-4 mRNA and protein in primary cultured dorsal root ganglion neurons.
Cell Mol Neurobiol. 2013 Apr; 33(3):337-46.CM

Abstract

Previous study has shown that there is a functional link between the transient receptor potential vanilloid type 1 (TRPV1) receptor and protease-activated receptor-4 (PAR4) in modulation of inflammation and pain. Capsaicin activation of TRPV1 is involved in enhancement of the expression of TRPV1 in mRNA and protein in dorsal root ganglion (DRG) in vivo. Whether capsaicin could influence expression of PAR4 in primary sensory neurons remains unknown. In the present study, expression of PAR4 in cultured rat DRG neurons was observed using immunofluorescence, real-time PCR and Western blots to examine whether increases in PAR4 mRNA and protein levels are induced by capsaicin treatment with or without pre-treatment of forskolin, a cyclic AMP/protein kinase A (cAMP/PKA) activator or PKA inhibitor fragment 14-22 (PKI14-22), a PKA inhibitor. Capsaicin treatment of cultured DRG neurons significantly increased the expression of PAR4 in mRNA and protein levels. The percentage of PAR4-, TRPV1-immunoreactive neurons and their co-localization in cultured DRG neurons increased significantly in the presence of capsaicin as compared with that in the absence of capsaicin. Compared with capsaicin-only group, pre-incubation with forskolin strongly enhanced the capsaicin-induced increase of PAR4 in mRNA and protein levels. Consistent with the involvement of PKA in the modulation of PAR4 expression, this evoked expression both at mRNA and protein levels was significantly inhibited after PKA was inhibited by pre-incubation with PKI14-22. Taken together, these results provide evidence that TRPV1 activation significantly increases the expression of PAR4 mRNA and protein levels in primary cultures of DRG neurons after capsaicin incubation. Effects of capsaicin on PAR4 expression appear to be mediated by cAMP/PKA signal pathways in DRG neurons.

Authors+Show Affiliations

Department of Anatomy, Taishan Medical University, Taian, 271000, Shandong Province, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23274964

Citation

Chen, Dan, et al. "Capsaicin Up-regulates Protease-activated Receptor-4 mRNA and Protein in Primary Cultured Dorsal Root Ganglion Neurons." Cellular and Molecular Neurobiology, vol. 33, no. 3, 2013, pp. 337-46.
Chen D, Wang Z, Zhang Z, et al. Capsaicin up-regulates protease-activated receptor-4 mRNA and protein in primary cultured dorsal root ganglion neurons. Cell Mol Neurobiol. 2013;33(3):337-46.
Chen, D., Wang, Z., Zhang, Z., Zhang, R., & Yu, L. (2013). Capsaicin up-regulates protease-activated receptor-4 mRNA and protein in primary cultured dorsal root ganglion neurons. Cellular and Molecular Neurobiology, 33(3), 337-46. https://doi.org/10.1007/s10571-012-9899-y
Chen D, et al. Capsaicin Up-regulates Protease-activated Receptor-4 mRNA and Protein in Primary Cultured Dorsal Root Ganglion Neurons. Cell Mol Neurobiol. 2013;33(3):337-46. PubMed PMID: 23274964.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Capsaicin up-regulates protease-activated receptor-4 mRNA and protein in primary cultured dorsal root ganglion neurons. AU - Chen,Dan, AU - Wang,Zhaojin, AU - Zhang,Zaifeng, AU - Zhang,Rui, AU - Yu,Lianfeng, Y1 - 2012/12/30/ PY - 2012/10/02/received PY - 2012/12/07/accepted PY - 2013/1/1/entrez PY - 2013/1/1/pubmed PY - 2013/9/5/medline SP - 337 EP - 46 JF - Cellular and molecular neurobiology JO - Cell Mol Neurobiol VL - 33 IS - 3 N2 - Previous study has shown that there is a functional link between the transient receptor potential vanilloid type 1 (TRPV1) receptor and protease-activated receptor-4 (PAR4) in modulation of inflammation and pain. Capsaicin activation of TRPV1 is involved in enhancement of the expression of TRPV1 in mRNA and protein in dorsal root ganglion (DRG) in vivo. Whether capsaicin could influence expression of PAR4 in primary sensory neurons remains unknown. In the present study, expression of PAR4 in cultured rat DRG neurons was observed using immunofluorescence, real-time PCR and Western blots to examine whether increases in PAR4 mRNA and protein levels are induced by capsaicin treatment with or without pre-treatment of forskolin, a cyclic AMP/protein kinase A (cAMP/PKA) activator or PKA inhibitor fragment 14-22 (PKI14-22), a PKA inhibitor. Capsaicin treatment of cultured DRG neurons significantly increased the expression of PAR4 in mRNA and protein levels. The percentage of PAR4-, TRPV1-immunoreactive neurons and their co-localization in cultured DRG neurons increased significantly in the presence of capsaicin as compared with that in the absence of capsaicin. Compared with capsaicin-only group, pre-incubation with forskolin strongly enhanced the capsaicin-induced increase of PAR4 in mRNA and protein levels. Consistent with the involvement of PKA in the modulation of PAR4 expression, this evoked expression both at mRNA and protein levels was significantly inhibited after PKA was inhibited by pre-incubation with PKI14-22. Taken together, these results provide evidence that TRPV1 activation significantly increases the expression of PAR4 mRNA and protein levels in primary cultures of DRG neurons after capsaicin incubation. Effects of capsaicin on PAR4 expression appear to be mediated by cAMP/PKA signal pathways in DRG neurons. SN - 1573-6830 UR - https://www.unboundmedicine.com/medline/citation/23274964/Capsaicin_up_regulates_protease_activated_receptor_4_mRNA_and_protein_in_primary_cultured_dorsal_root_ganglion_neurons_ L2 - https://doi.org/10.1007/s10571-012-9899-y DB - PRIME DP - Unbound Medicine ER -