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

被引:15
作者
Castillo, C. [1 ,2 ]
Norcini, M. [1 ,3 ]
Baquero-Buitrago, J. [1 ]
Levacic, D. [1 ]
Medina, R. [2 ]
Montoya-Gacharna, J. V. [1 ]
Blanck, T. J. J. [1 ,4 ]
Dubois, M. [1 ]
Recio-Pinto, E. [1 ,5 ]
机构
[1] NYU, Langone Med Ctr, Dept Anesthesiol, New York, NY 10016 USA
[2] Inst Estudios Avanzados IDEA, Caracas, Venezuela
[3] Univ Florence, Dept Clin & Preclin Pharmacol, I-50121 Florence, Italy
[4] NYU, Langone Med Ctr, Dept Physiol & Neurosci, New York, NY 10016 USA
[5] NYU, Langone Med Ctr, Dept Pharmacol, New York, NY 10016 USA
关键词
primary sensory neurons; substance P; NMDA; neurokinin receptor; protein kinase C; bisindolylmaleimide; PRIMARY SENSORY NEURONS; NMDA RECEPTOR ANTAGONISTS; NEUROPATHIC PAIN; NR2B SUBUNIT; HORN NEURONS; DRG NEURONS; TYROSINE PHOSPHORYLATION; INTRACELLULAR CALCIUM; THERMAL HYPERALGESIA; INFLAMED RATS;
D O I
10.1016/j.neuroscience.2010.12.040
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 E-2 (PGE(2)) or both NGF+PGE(2). 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-Pro(4), D- Trp(7.9)]-SP (4-11)) and by the protein kinase C (PKC) blocker bisindolylmaleimide I (BIM); and correlated with the phosphorylation of PKC epsilon. The Nk1r agonist [Sar(9), Met(O-2)(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-PKC epsilon. 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. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:308 / 320
页数:13
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