Journal of Neurophysiology, Vol 68, Issue 1 265-286, Copyright © 1992 by APS

ARTICLES

Modulation of excitatory amino acid responses in rat dorsal horn neurons by tachykinins

K. I. Rusin, P. D. Ryu and M. Randic
Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames 50011.

1. In freshly isolated spinal dorsal horn (DH) neurons (laminae I-III) of the young rat, the effects of tachykinins (substance P, neurokinin A) on inward current induced by excitatory amino acids were studied under whole-cell voltage-clamp conditions. 2. When the cells were clamped to a holding potential of -60 mV, a simultaneous application of N-methyl-D-aspartate (NMDA) (10(-4) M) and substance P (SP) (2 x 10(-9)-10(-7) M) for 10 s reversibly enhanced (by 129.6 +/- 8.2%, mean +/- SE) the peak amplitude of the initial transient component of the NMDA-induced current in approximately 60% of the examined cells and reduced it (to 83.3 +/- 2.7%) in 27% of the cells. In addition, SP produced an increase (by 133.6 +/- 11.7%) or a small decrease (to 85.9 +/- 1.4%) in the steady-state component of the NMDA response. In difference to SP, a simultaneous application of NMDA (10(-4) M) and neurokinin A (NKA) (10(-10)-10(-7) M) reversibly suppressed (to 86.8 +/- 2.1%) the peak amplitude of the NMDA-induced current in 75% of the examined cells. 3. The NMDA-induced currents were modulated by tachykinins not only during the coadministration but up to 20 min after the removal of the peptide. SP potentiated the initial peak NMDA current by 147.9 +/- 8.1% in 78% of examined cells and decreased it (76.3 +/- 5.7%) in 11% of cells. The potentiating effect was concentration-dependent (range: 10(-11)-10(-8) M) and reversible, but it was reduced with repeated applications. In addition, SP increased (by 125.4 +/- 3.6%) or reduced (to 86.0 +/- 1.8%) the steady-state component of the NMDA response. 4. When the single DH neurons were exposed to SP or NKA for 30 s-7 min before the testing of the NMDA responses, tachykinins had two distinct effects on the peak amplitude of the transient component of the NMDA-induced current, consisting of an initial depression (SP: to 64.8 +/- 2.1%; NKA: to 76.3 +/- 4.4%) followed by a potentiation (SP: by 146.6 +/- 6.8%; NKA: by 178.4 +/- 35.2%). The enhancing effect in some cells lasted less than or equal to 1 h. 5. A claimed novel nonselective tachykinin antagonist, spantide II (10(-8) M) coadministered with NMDA (10(-4) M), slightly depressed the peak component of NMDA-induced current. In addition, it effectively blocked the SP-induced potentiation of the responses of DH neurons to NMDA.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				P. M. Schmitt and M. P. Kaufman Estrogen's attenuating effect on the exercise pressor reflex is more opioid dependent in gonadally intact than in ovariectomized female cats J Appl Physiol, February 1, 2005; 98(2): 633 - 639. [Abstract] [Full Text] [PDF]

				C. Marchetti and A. Nistri Neuronal Bursting Induced by NK3 Receptor Activation in the Neonatal Rat Spinal Cord In Vitro J Neurophysiol, December 1, 2001; 86(6): 2939 - 2950. [Abstract] [Full Text] [PDF]

				I. D. Hentall, B. R. Noga, and J. Sagen Spinal Allografts of Adrenal Medulla Block Nociceptive Facilitation in the Dorsal Horn J Neurophysiol, April 1, 2001; 85(4): 1788 - 1792. [Abstract] [Full Text] [PDF]

				X. Zou, Q. Lin, and W. D. Willis Enhanced Phosphorylation of NMDA Receptor 1 Subunits in Spinal Cord Dorsal Horn and Spinothalamic Tract Neurons after Intradermal Injection of Capsaicin in Rats J. Neurosci., September 15, 2000; 20(18): 6989 - 6997. [Abstract] [Full Text] [PDF]

				H. Ogawa, K. Hasegawa, and T. Nakamura Action of Calcitonin Gene-related Peptide (CGRP) and Substance P on Neurons in the Insular Cortex and the Modulation of Taste Responses in the Rat Chem Senses, August 1, 2000; 25(4): 351 - 359. [Abstract] [Full Text] [PDF]

				D. Parker, W. Zhang, and S. Grillner Substance P Modulates NMDA Responses and Causes Long-Term Protein Synthesis-Dependent Modulation of the Lamprey Locomotor Network J. Neurosci., June 15, 1998; 18(12): 4800 - 4813. [Abstract] [Full Text] [PDF]

				A. Zimmer, A. M. Zimmer, J. Baffi, T. Usdin, K. Reynolds, M. Konig, M. Palkovits, and E. Mezey Hypoalgesia in mice with a targeted deletion of the tachykinin 1 gene PNAS, March 3, 1998; 95(5): 2630 - 2635. [Abstract] [Full Text] [PDF]