![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
U Brauneis, M Oz, RW Peoples, FF Weight and L Zhang
Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Dynorphin is an endogenous ligand for kappa-opioid receptors. We investigated the effect of dynorphin 1-13 on different heteromeric subunits of recombinant mouse N-methyl-D-aspartate (NMDA) receptors expressed in Xenopus oocytes by using voltage-clamp recording methods. Dynorphin inhibited the NMDA-activated currents of all heteromeric NMDA receptor subunits tested. The different NMDA receptor subunits, however, exhibited a differential sensitivity to dynorphin. For the epsilon-1/zeta-1 subunit combination the EC50 was 19 microM; the other NMDA receptor subunit combinations were less sensitive to dynorphin and had the following order of sensitivity: epsilon-2/zeta-1 > epsilon- 4/zeta-1 > epsilon-3/zeta-1. Inhibition of NMDA-activated currents by dynorphin was not competitive with NMDA, and was voltage-independent. NMDA-activated currents were not affected by the synthetic kappa-opioid receptor agonist U50488 trans-3, 4-dichloro-N-methyl-N-[2-(1- pyrrolidinyl)-cyclohexyl]benzene-acetamide, the specific kappa-opioid receptor antagonist nor-binaltorphimine1 or the nonspecific opioid receptor antagonist naloxone. In addition, nor-binaltorphimine1 or naloxone did not attenuate dynorphin inhibition of NMDA-activated current. The observations suggest that dynorphin inhibition of NMDA receptor function is mediated by an interaction of dynorphin with NMDA receptors, rather than an action involving kappa-opioid receptors. The data also show that different heteromeric NMDA receptor subunits exhibit a differential sensitivity to dynorphin.
This article has been cited by other articles:
|
|
 |
|
  T. M. Laughlin, A. A. Larson, and G. L. Wilcox Mechanisms of Induction of Persistent Nociception by Dynorphin J. Pharmacol. Exp. Ther., October 1, 2001; 299(1): 6 - 11. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lai, M. H. Ossipov, T. W. Vanderah, T. P. Malan Jr., and F. Porreca Neuropathic Pain: The Paradox of Dynorphin Mol. Interv., August 1, 2001; 1(3): 160 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Tang, R. M. Lynch, F. Porreca, and J. Lai Dynorphin A Elicits an Increase in Intracellular Calcium in Cultured Neurons Via a Non-Opioid, Non-NMDA Mechanism J Neurophysiol, May 1, 2000; 83(5): 2610 - 2615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Tang, R. Gandhoke, A. Burritt, V. J. Hruby, F. Porreca, and J. Lai High-Affinity Interaction of (des-Tyrosyl)Dynorphin A(2-17) with NMDA Receptors J. Pharmacol. Exp. Ther., November 1, 1999; 291(2): 760 - 765. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. Dingledine, K. Borges, D. Bowie, and S. F. Traynelis The Glutamate Receptor Ion Channels Pharmacol. Rev., March 1, 1999; 51(1): 7 - 62. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. A. Abdulla and P. A. Smith Nociceptin Inhibits T-Type Ca2+ Channel Current in Rat Sensory Neurons by a G-Protein-Independent Mechanism J. Neurosci., November 15, 1997; 17(22): 8721 - 8728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhang, R. W. Peoples, M. Oz, J. Harvey-White, F. F. Weight, and U. Brauneis Potentiation of NMDA Receptor-Mediated Responses by Dynorphin at Low Extracellular Glycine Concentrations J Neurophysiol, August 1, 1997; 78(2): 582 - 590. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
