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Sustained potentiation by substance P of NMDA-activated current in rat primary sensory neurons.
Brain Res. 2004 Jun 04; 1010(1-2):117-26.BR

Abstract

This study aimed to explore the modulatory effect of substance P (SP) on the current response mediated by N-methyl-D-aspartate (NMDA) receptor in rat primary sensory neurons and its time course using whole-cell patch clamp technique. The majority of neurons (179/213, 84.0%) examined were sensitive to NMDA (0.1-1000 microM) with an inward current, and a proportion of the NMDA-sensitive neurons also responded to SP (78/98, 80.0%) with an inward current. Pretreatment with SP potentiated the NMDA-activated current (INMDA) in a non-competitive manner, which is shown in that SP shifted the concentration-response curve for NMDA upwards compared with the control; the maximal value of INMDA increased fourfold, while the EC50 values for both curves were very close (28 vs. 30 microM). Furthermore, this potentiating effect was time-dependent: the amplitude of INMDA reached its maximum 20 min after SP preapplication, and thereafter maintained a steady level of about 2-3 times its control for 2 or even 3 h. This sustained potentiation by SP of INMDA could be blocked by extracellular application of WIN51708, a selective non-peptide antagonist of NK-1 receptor; and abolished by intracellular application of either BAPTA, or H-7, or KN-93. Though NMDA applied alone also induced a short-term (less than 20 min) self-potentiation of INMDA, it could be abolished by intracellular dialysis of BAPTA or KN-93 completely. As is known, the cell body of dorsal root ganglion (DRG) neurons is generally used as an accessible model for studying the characteristics of the membrane of primary afferent terminals in the dorsal horn of spinal cord. Therefore, these results may offer a clue to the explanation of the symptoms of chronic pain.

Authors+Show Affiliations

Department of Molecular and Cellular Neurobiology, Tongji Medical College of Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei 430030, PR China.No 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

15126124

Citation

Wu, Zi-Zhen, et al. "Sustained Potentiation By Substance P of NMDA-activated Current in Rat Primary Sensory Neurons." Brain Research, vol. 1010, no. 1-2, 2004, pp. 117-26.
Wu ZZ, Guan BC, Li ZW, et al. Sustained potentiation by substance P of NMDA-activated current in rat primary sensory neurons. Brain Res. 2004;1010(1-2):117-26.
Wu, Z. Z., Guan, B. C., Li, Z. W., Yang, Q., Liu, C. J., & Chen, J. G. (2004). Sustained potentiation by substance P of NMDA-activated current in rat primary sensory neurons. Brain Research, 1010(1-2), 117-26.
Wu ZZ, et al. Sustained Potentiation By Substance P of NMDA-activated Current in Rat Primary Sensory Neurons. Brain Res. 2004 Jun 4;1010(1-2):117-26. PubMed PMID: 15126124.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sustained potentiation by substance P of NMDA-activated current in rat primary sensory neurons. AU - Wu,Zi-Zhen, AU - Guan,Bing-Cai, AU - Li,Zhi-Wang, AU - Yang,Qing, AU - Liu,Chang-Jin, AU - Chen,Jian-Guo, PY - 2004/03/01/accepted PY - 2004/5/6/pubmed PY - 2004/9/2/medline PY - 2004/5/6/entrez SP - 117 EP - 26 JF - Brain research JO - Brain Res VL - 1010 IS - 1-2 N2 - This study aimed to explore the modulatory effect of substance P (SP) on the current response mediated by N-methyl-D-aspartate (NMDA) receptor in rat primary sensory neurons and its time course using whole-cell patch clamp technique. The majority of neurons (179/213, 84.0%) examined were sensitive to NMDA (0.1-1000 microM) with an inward current, and a proportion of the NMDA-sensitive neurons also responded to SP (78/98, 80.0%) with an inward current. Pretreatment with SP potentiated the NMDA-activated current (INMDA) in a non-competitive manner, which is shown in that SP shifted the concentration-response curve for NMDA upwards compared with the control; the maximal value of INMDA increased fourfold, while the EC50 values for both curves were very close (28 vs. 30 microM). Furthermore, this potentiating effect was time-dependent: the amplitude of INMDA reached its maximum 20 min after SP preapplication, and thereafter maintained a steady level of about 2-3 times its control for 2 or even 3 h. This sustained potentiation by SP of INMDA could be blocked by extracellular application of WIN51708, a selective non-peptide antagonist of NK-1 receptor; and abolished by intracellular application of either BAPTA, or H-7, or KN-93. Though NMDA applied alone also induced a short-term (less than 20 min) self-potentiation of INMDA, it could be abolished by intracellular dialysis of BAPTA or KN-93 completely. As is known, the cell body of dorsal root ganglion (DRG) neurons is generally used as an accessible model for studying the characteristics of the membrane of primary afferent terminals in the dorsal horn of spinal cord. Therefore, these results may offer a clue to the explanation of the symptoms of chronic pain. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/15126124/Sustained_potentiation_by_substance_P_of_NMDA_activated_current_in_rat_primary_sensory_neurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006899304004305 DB - PRIME DP - Unbound Medicine ER -