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The N-methyl-D-aspartate-evoked cytoplasmic calcium increase in adult rat dorsal root ganglion neuronal somata was potentiated by substance P pretreatment in a protein kinase C-dependent manner.
Neuroscience. 2011 Mar 17; 177:308-20.N

Abstract

The involvement of substance P (SP) in neuronal sensitization through the activation of the neurokinin-1-receptor (NK1r) in postsynaptic dorsal horn neurons has been well established. In contrast, the role of SP and NK1r in primary sensory dorsal root ganglion (DRG) neurons, in particular in the soma, is not well understood. In this study, we evaluated whether SP modulated the NMDA-evoked transient increase in cytoplasmic Ca2+ ([Ca2+]cyt) in the soma of dissociated adult DRG neurons. Cultures were treated with nerve growth factor (NGF), prostaglandin E2 (PGE2) or both NGF+PGE2. Treatment with NGF+PGE2 increased the percentage of N-methyl-D-aspartate (NMDA) responsive neurons. There was no correlation between the percentage of NMDA responsive neurons and the level of expression of the NR1 and NR2B subunits of the NMDA receptor or of the NK1r. Pretreatment with SP did not alter the percentage of NMDA responsive neurons; while it potentiated the NMDA-evoked [Ca2+]cyt transient by increasing its magnitude and by prolonging the period during which small- and some medium-sized neurons remained NMDA responsive. The SP-mediated potentiation was blocked by the SP-antagonist ([D-Pro4, D-Trp7,9]-SP (4-11)) and by the protein kinase C (PKC) blocker bisindolylmaleimide I (BIM); and correlated with the phosphorylation of PKCε. The Nk1r agonist [Sar9, Met(O2)11]-SP (SarMet-SP) also potentiated the NMDA-evoked [Ca2+]cyt transient. Exposure to SP or SarMet-SP produced a rapid increase in the labeling of phosphorylated-PKCε. In none of the conditions we detected phosphorylation of the NR2B subunit at Ser-1303. Phosphorylation of the NR2B subunit at Tyr1472 was enhanced to a similar extent in cells exposed to NMDA, SP or NMDA+SP, and that enhancement was blocked by BIM. Our findings suggest that NGF and PGE2 may contribute to the injury-evoked sensitization of DRG neurons in part by enhancing their NMDA-evoked [Ca2+]cyt transient in all sized DRG neurons; and that SP may further contribute to the DRG sensitization by enhancing and prolonging the NMDA-evoked increase in [Ca2+]cyt in small- and medium-sized DRG neurons.

Authors+Show Affiliations

Department of Anesthesiology, New York University (NYU) Langone Medical Center, NY 10016, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

21215796

Citation

Castillo, C, et al. "The N-methyl-D-aspartate-evoked Cytoplasmic Calcium Increase in Adult Rat Dorsal Root Ganglion Neuronal Somata Was Potentiated By Substance P Pretreatment in a Protein Kinase C-dependent Manner." Neuroscience, vol. 177, 2011, pp. 308-20.
Castillo C, Norcini M, Baquero-Buitrago J, et al. The N-methyl-D-aspartate-evoked cytoplasmic calcium increase in adult rat dorsal root ganglion neuronal somata was potentiated by substance P pretreatment in a protein kinase C-dependent manner. Neuroscience. 2011;177:308-20.
Castillo, C., Norcini, M., Baquero-Buitrago, J., Levacic, D., Medina, R., Montoya-Gacharna, J. V., Blanck, T. J., Dubois, M., & Recio-Pinto, E. (2011). The N-methyl-D-aspartate-evoked cytoplasmic calcium increase in adult rat dorsal root ganglion neuronal somata was potentiated by substance P pretreatment in a protein kinase C-dependent manner. Neuroscience, 177, 308-20. https://doi.org/10.1016/j.neuroscience.2010.12.040
Castillo C, et al. The N-methyl-D-aspartate-evoked Cytoplasmic Calcium Increase in Adult Rat Dorsal Root Ganglion Neuronal Somata Was Potentiated By Substance P Pretreatment in a Protein Kinase C-dependent Manner. Neuroscience. 2011 Mar 17;177:308-20. PubMed PMID: 21215796.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The N-methyl-D-aspartate-evoked cytoplasmic calcium increase in adult rat dorsal root ganglion neuronal somata was potentiated by substance P pretreatment in a protein kinase C-dependent manner. AU - Castillo,C, AU - Norcini,M, AU - Baquero-Buitrago,J, AU - Levacic,D, AU - Medina,R, AU - Montoya-Gacharna,J V, AU - Blanck,T J J, AU - Dubois,M, AU - Recio-Pinto,E, Y1 - 2011/01/06/ PY - 2010/11/05/received PY - 2010/12/16/revised PY - 2010/12/21/accepted PY - 2011/1/11/entrez PY - 2011/1/11/pubmed PY - 2012/1/20/medline SP - 308 EP - 20 JF - Neuroscience JO - Neuroscience VL - 177 N2 - The involvement of substance P (SP) in neuronal sensitization through the activation of the neurokinin-1-receptor (NK1r) in postsynaptic dorsal horn neurons has been well established. In contrast, the role of SP and NK1r in primary sensory dorsal root ganglion (DRG) neurons, in particular in the soma, is not well understood. In this study, we evaluated whether SP modulated the NMDA-evoked transient increase in cytoplasmic Ca2+ ([Ca2+]cyt) in the soma of dissociated adult DRG neurons. Cultures were treated with nerve growth factor (NGF), prostaglandin E2 (PGE2) or both NGF+PGE2. Treatment with NGF+PGE2 increased the percentage of N-methyl-D-aspartate (NMDA) responsive neurons. There was no correlation between the percentage of NMDA responsive neurons and the level of expression of the NR1 and NR2B subunits of the NMDA receptor or of the NK1r. Pretreatment with SP did not alter the percentage of NMDA responsive neurons; while it potentiated the NMDA-evoked [Ca2+]cyt transient by increasing its magnitude and by prolonging the period during which small- and some medium-sized neurons remained NMDA responsive. The SP-mediated potentiation was blocked by the SP-antagonist ([D-Pro4, D-Trp7,9]-SP (4-11)) and by the protein kinase C (PKC) blocker bisindolylmaleimide I (BIM); and correlated with the phosphorylation of PKCε. The Nk1r agonist [Sar9, Met(O2)11]-SP (SarMet-SP) also potentiated the NMDA-evoked [Ca2+]cyt transient. Exposure to SP or SarMet-SP produced a rapid increase in the labeling of phosphorylated-PKCε. In none of the conditions we detected phosphorylation of the NR2B subunit at Ser-1303. Phosphorylation of the NR2B subunit at Tyr1472 was enhanced to a similar extent in cells exposed to NMDA, SP or NMDA+SP, and that enhancement was blocked by BIM. Our findings suggest that NGF and PGE2 may contribute to the injury-evoked sensitization of DRG neurons in part by enhancing their NMDA-evoked [Ca2+]cyt transient in all sized DRG neurons; and that SP may further contribute to the DRG sensitization by enhancing and prolonging the NMDA-evoked increase in [Ca2+]cyt in small- and medium-sized DRG neurons. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/21215796/The_N_methyl_D_aspartate_evoked_cytoplasmic_calcium_increase_in_adult_rat_dorsal_root_ganglion_neuronal_somata_was_potentiated_by_substance_P_pretreatment_in_a_protein_kinase_C_dependent_manner_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(10)01645-3 DB - PRIME DP - Unbound Medicine ER -