![[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}
|
|
|
|
|
||
TJ Wilding and JE Huettner
Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110.
Whole-cell recordings were used to study the antagonism of alpha-amino- 3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-preferring and kainate-preferring receptors by 2,3-benzodiazepines. Current through kainate-preferring receptors was recorded in rat dorsal root ganglion (DRG) neuron-s, whereas AMPA receptor current was measured in cultured neurons from rat cerebral cortex. In both cell types 2,3- benzodiazepines produced noncompetitive inhibition; however, antagonist potency was much higher against AMPA-preferring receptors than against kainate receptors. The most potent compound, 1-(4-aminophenyl)-3- methylcarbamyl-4-methyl-7,8- methylenedioxy-3,4-dihydro-5H-2,3- benzodiazepine (GYKI 53655), blocked AMPA receptor currents with an IC50 of approximately 1 microM. A second benzodiazepine, 1-(4- aminophenyl)-4-methyl-7,8- methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466), was about 20-fold less potent at AMPA receptors (IC50 = 18 microM). Both drugs were markedly weaker against kainate currents in DRG neurons. At 200 microM, the highest concentration tested, GYKI 53655 and GYKI 52466 produced only 30-40% inhibition in DRG cells, suggesting that for both compounds the IC50 against kainate receptors is > 200 microM. Our study suggests that GYKI 53655, at a concentration of approximately 10 microM, should produce > 90% block of AMPA- preferring receptors but < 5% inhibition of kainate-preferring receptors. Because the antagonism by this drug is noncompetitive, its effectiveness should not be influenced by phasic changes in transmitter concentration, making it an ideal compound for functional studies of the role of kainate and AMPA receptors in synaptic transmission.
This article has been cited by other articles:
|
|
 |
|
  T. A. Vander Jagt, J. A. Connor, and C. W. Shuttleworth Localized Loss of Ca2+ Homeostasis in Neuronal Dendrites Is a Downstream Consequence of Metabolic Compromise during Extended NMDA Exposures J. Neurosci., May 7, 2008; 28(19): 5029 - 5039. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Crepel and H. Daniel Developmental Changes in Agonist-Induced Retrograde Signaling at Parallel Fiber Purkinje Cell Synapses: Role of Calcium-Induced Calcium Release J Neurophysiol, November 1, 2007; 98(5): 2550 - 2565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Vigh and H. von Gersdorff Prolonged Reciprocal Signaling via NMDA and GABA Receptors at a Retinal Ribbon Synapse J. Neurosci., December 7, 2005; 25(49): 11412 - 11423. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hamann, D. J. Rossi, C. Mohr, A. L. Andrade, and D. Attwell The electrical response of cerebellar Purkinje neurons to simulated ischaemia Brain, October 1, 2005; 128(10): 2408 - 2420. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-J. Wu, M.-G. Zhao, H. Toyoda, S. W. Ko, and M. Zhuo Kainate Receptor-Mediated Synaptic Transmission in the Adult Anterior Cingulate Cortex J Neurophysiol, September 1, 2005; 94(3): 1805 - 1813. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Maingret, S. E Lauri, T. Taira, and J. T. R Isaac Profound regulation of neonatal CA1 rat hippocampal GABAergic transmission by functionally distinct kainate receptor populations J. Physiol., August 15, 2005; 567(1): 131 - 142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ko, M.-G. Zhao, H. Toyoda, C.-S. Qiu, and M. Zhuo Altered Behavioral Responses to Noxious Stimuli and Fear in Glutamate Receptor 5 (GluR5)- or GluR6-Deficient Mice J. Neurosci., January 26, 2005; 25(4): 977 - 984. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Christensen, A. V. Paternain, S. Selak, P. K. Ahring, and J. Lerma A Mosaic of Functional Kainate Receptors in Hippocampal Interneurons J. Neurosci., October 13, 2004; 24(41): 8986 - 8993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Seifert, K. Huttmann, J. Schramm, and C. Steinhauser Enhanced Relative Expression of Glutamate Receptor 1 Flip AMPA Receptor Subunits in Hippocampal Astrocytes of Epilepsy Patients with Ammon's Horn Sclerosis J. Neurosci., February 25, 2004; 24(8): 1996 - 2003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Gryder and M. A. Rogawski Selective Antagonism of GluR5 Kainate-Receptor-Mediated Synaptic Currents by Topiramate in Rat Basolateral Amygdala Neurons J. Neurosci., August 6, 2003; 23(18): 7069 - 7074. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Feng, P. Molnar, and J. V. Nadler Short-Term Frequency-Dependent Plasticity at Recurrent Mossy Fiber Synapses of the Epileptic Brain J. Neurosci., June 15, 2003; 23(12): 5381 - 5390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. M. Braga, V. Aroniadou-Anderjaska, J. Xie, and H. Li Bidirectional Modulation of GABA Release by Presynaptic Glutamate Receptor 5 Kainate Receptors in the Basolateral Amygdala J. Neurosci., January 15, 2003; 23(2): 442 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Kerchner, T. J. Wilding, J. E. Huettner, and M. Zhuo Kainate Receptor Subunits Underlying Presynaptic Regulation of Transmitter Release in the Dorsal Horn J. Neurosci., September 15, 2002; 22(18): 8010 - 8017. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lerma, A. V. Paternain, A. Rodriguez-Moreno, and J. C. Lopez-Garcia Molecular Physiology of Kainate Receptors Physiol Rev, July 1, 2001; 81(3): 971 - 998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Frerking, D. Schmitz, Q. Zhou, J. Johansen, and R. A. Nicoll Kainate Receptors Depress Excitatory Synaptic Transmission at CA3{right-arrow}CA1 Synapses in the Hippocampus via a Direct Presynaptic Action J. Neurosci., May 1, 2001; 21(9): 2958 - 2966. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. S. Menniti, B. L. Chenard, M. B. Collins, M. F. Ducat, M. L. Elliott, F. E. Ewing, J. I. Huang, K. A. Kelly, J. T. Lazzaro, M. J. Pagnozzi, et al. Characterization of the Binding Site for a Novel Class of Noncompetitive alpha -Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptor Antagonists Mol. Pharmacol., April 13, 2001; 58(6): 1310 - 1317. [Abstract] [Full Text]
|
|
|
|
 |
|
 I. Bureau, S. Dieudonne, F. Coussen, and C. Mulle Kainate receptor-mediated synaptic currents in cerebellar Golgi cells are not shaped by diffusion of glutamate PNAS, June 6, 2000; 97(12): 6838 - 6843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rodriguez-Moreno, J. C. Lopez-Garcia, and J. Lerma Two populations of kainate receptors with separate signaling mechanisms in hippocampal interneurons PNAS, February 1, 2000; 97(3): 1293 - 1298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S. Engelman, T. B. Allen, and A. B. MacDermott The Distribution of Neurons Expressing Calcium-Permeable AMPA Receptors in the Superficial Laminae of the Spinal Cord Dorsal Horn J. Neurosci., March 15, 1999; 19(6): 2081 - 2089. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
I. Bureau, S. Bischoff, S. F. Heinemann, and C. Mulle Kainate Receptor-Mediated Responses in the CA1 Field of Wild-Type and GluR6-Deficient Mice J. Neurosci., January 15, 1999; 19(2): 653 - 663. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Wahl, C. Anker, S. F. Traynelis, J. Egebjerg, J. S. Rasmussen, P. Krogsgaard-Larsen, and U. Madsen Antagonist Properties of a Phosphono Isoxazole Amino Acid at Glutamate R1-4 (R,S)-2-Amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic Acid Receptor Subtypes Mol. Pharmacol., March 1, 1998; 53(3): 590 - 596. [Abstract] [Full Text]
|
|
|
|
|
|
T. J. Wilding and J. E. Huettner Activation and Desensitization of Hippocampal Kainate Receptors J. Neurosci., April 15, 1997; 17(8): 2713 - 2721. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. D. Lukasiewicz, J. A. Wilson, and J. E. Lawrence AMPA-Preferring Receptors Mediate Excitatory Synaptic Inputs to Retinal Ganglion Cells J Neurophysiol, January 1, 1997; 77(1): 57 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-M. Zhou, Z.-Q. Gu, A. M. Costa, K. A. Yamada, P. E. Mansson, T. Giordano, P. Skolnick, and K. A. Jones (2S,4R)-4-Methylglutamic Acid (SYM 2081): A Selective, High-Affinity Ligand for Kainate Receptors J. Pharmacol. Exp. Ther., January 1, 1997; 280(1): 422 - 427. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
