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Endothelin-1 enhances capsaicin-evoked intracellular Ca2+ response via activation of endothelin a receptor in a protein kinase Cepsilon-dependent manner in dorsal root ganglion neurons.
Neuroscience. 2006 Feb; 137(3):949-60.N

Abstract

Increasing evidence indicates that endothelin-1 has a role for peripheral nociceptive signaling in animals and humans. However, the mechanisms of the nociceptive effects of endothelin-1 have not been fully understood. The current study investigated the effects of endothelin-1 on the capsaicin-evoked intracellular Ca2+ response of cultured adult mice dorsal root ganglion neurons. Dorsal root ganglia were harvested from adult male C57B6N mice and were cultured. With a digital image analysis system, we detected the [Ca2+]i image of cultured dorsal root ganglion cells after loading with Fura-2 acetoxymethyl. In addition, co-localization of protein kinase Cepsilon with transient receptor potential V1 and the translocation of protein kinase Cepsilon were investigated using immunohistochemical methods. Endothelin-1 (10 nM) enhanced an increase in [Ca2+]i by capsaicin (10 nM) from 87.6+/-11.6 nM to 414.8+/-62.3 nM (71 of 156 neurons). The inhibition of endothelin A receptor (BQ-123) significantly suppressed the enhancing effect of endothelin-1. In addition, a nonselective protein kinase C inhibitor (bisindolylmaleimide I) significantly suppressed the enhancing effect of endothelin-1. A myristoyl-tagged membrane-permeant-protein kinase Cepsilon V1-2 inhibitory peptide also significantly suppressed the enhancing effect of endothelin-1. In the immunocytochemical study, protein kinase Cepsilon immunoreactivity was found in most of transient receptor potential V1-positive neurons. After endothelin-1 application, protein kinase Cepsilon immunoreactivity was observed to be translocated from the cytosol to the cell membrane in transient receptor potential V1-positive neurons. Our results indicate that endothelin-1 enhances the response of dorsal root ganglion neurons to capsaicin in a protein kinase Cepsilon-dependent manner. Our findings may lead to a new strategy to treat pain associated with endothelin-1.

Authors+Show Affiliations

Department of Anesthesiology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido 060-8543, Japan.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

16298080

Citation

Yamamoto, H, et al. "Endothelin-1 Enhances Capsaicin-evoked Intracellular Ca2+ Response Via Activation of Endothelin a Receptor in a Protein Kinase Cepsilon-dependent Manner in Dorsal Root Ganglion Neurons." Neuroscience, vol. 137, no. 3, 2006, pp. 949-60.
Yamamoto H, Kawamata T, Ninomiya T, et al. Endothelin-1 enhances capsaicin-evoked intracellular Ca2+ response via activation of endothelin a receptor in a protein kinase Cepsilon-dependent manner in dorsal root ganglion neurons. Neuroscience. 2006;137(3):949-60.
Yamamoto, H., Kawamata, T., Ninomiya, T., Omote, K., & Namiki, A. (2006). Endothelin-1 enhances capsaicin-evoked intracellular Ca2+ response via activation of endothelin a receptor in a protein kinase Cepsilon-dependent manner in dorsal root ganglion neurons. Neuroscience, 137(3), 949-60.
Yamamoto H, et al. Endothelin-1 Enhances Capsaicin-evoked Intracellular Ca2+ Response Via Activation of Endothelin a Receptor in a Protein Kinase Cepsilon-dependent Manner in Dorsal Root Ganglion Neurons. Neuroscience. 2006;137(3):949-60. PubMed PMID: 16298080.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endothelin-1 enhances capsaicin-evoked intracellular Ca2+ response via activation of endothelin a receptor in a protein kinase Cepsilon-dependent manner in dorsal root ganglion neurons. AU - Yamamoto,H, AU - Kawamata,T, AU - Ninomiya,T, AU - Omote,K, AU - Namiki,A, Y1 - 2005/11/17/ PY - 2005/06/07/received PY - 2005/08/30/revised PY - 2005/09/24/accepted PY - 2005/11/22/pubmed PY - 2006/4/13/medline PY - 2005/11/22/entrez SP - 949 EP - 60 JF - Neuroscience JO - Neuroscience VL - 137 IS - 3 N2 - Increasing evidence indicates that endothelin-1 has a role for peripheral nociceptive signaling in animals and humans. However, the mechanisms of the nociceptive effects of endothelin-1 have not been fully understood. The current study investigated the effects of endothelin-1 on the capsaicin-evoked intracellular Ca2+ response of cultured adult mice dorsal root ganglion neurons. Dorsal root ganglia were harvested from adult male C57B6N mice and were cultured. With a digital image analysis system, we detected the [Ca2+]i image of cultured dorsal root ganglion cells after loading with Fura-2 acetoxymethyl. In addition, co-localization of protein kinase Cepsilon with transient receptor potential V1 and the translocation of protein kinase Cepsilon were investigated using immunohistochemical methods. Endothelin-1 (10 nM) enhanced an increase in [Ca2+]i by capsaicin (10 nM) from 87.6+/-11.6 nM to 414.8+/-62.3 nM (71 of 156 neurons). The inhibition of endothelin A receptor (BQ-123) significantly suppressed the enhancing effect of endothelin-1. In addition, a nonselective protein kinase C inhibitor (bisindolylmaleimide I) significantly suppressed the enhancing effect of endothelin-1. A myristoyl-tagged membrane-permeant-protein kinase Cepsilon V1-2 inhibitory peptide also significantly suppressed the enhancing effect of endothelin-1. In the immunocytochemical study, protein kinase Cepsilon immunoreactivity was found in most of transient receptor potential V1-positive neurons. After endothelin-1 application, protein kinase Cepsilon immunoreactivity was observed to be translocated from the cytosol to the cell membrane in transient receptor potential V1-positive neurons. Our results indicate that endothelin-1 enhances the response of dorsal root ganglion neurons to capsaicin in a protein kinase Cepsilon-dependent manner. Our findings may lead to a new strategy to treat pain associated with endothelin-1. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/16298080/Endothelin_1_enhances_capsaicin_evoked_intracellular_Ca2+_response_via_activation_of_endothelin_a_receptor_in_a_protein_kinase_Cepsilon_dependent_manner_in_dorsal_root_ganglion_neurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(05)01094-8 DB - PRIME DP - Unbound Medicine ER -