![[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}
|
|
|
|
|
||
T Hayashi, A Kagaya, M Takebayashi, M Shimizu, Y Uchitomi, N Motohashi and S Yamawaki
Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, Japan.
Despite substantial data on radioligand binding to the sigma receptor, neither the physiologic function nor the intracellular mechanism of this receptor is known. In this study, we examined the effect of sigma ligands on Ca++ influx induced by N-methyl-D-aspartate (NMDA) in single primary cultured rat frontal cortical neurons with fluorescence video microscopy. All sigma ligands tested reduced the NMDA-induced increase in intracellular Ca++ concentration ([Ca++]i) in a dose-dependent manner with IC50 values in the low micromolar range. Inhibition by haloperidol and (+)-N-cyclopropylmethyl-N-methyl-1,4-diphenyl-1-ethyl- but-3-en-1-ylam ine hydrochloride (JO1784) was noncompetitive; but, exogenous glycine (100 microM) did not alter their IC50 values. In addition, haloperidol (1 microM) enhanced Mg+(+)-mediated inhibition of the NMDA-induced [Ca++]i increase (IC50 = 0.45 +/- 0.01 mM vs. an IC50 = 0.98 +/- 0.06 mM for Mg++ alone). Selective sigma receptor ligands (JO1784, (+)-pentazocine) caused a greater reduction of the sustained phase of the Ca++ response to NMDA, whereas haloperidol and DTG reduced both the initial and sustained phase of the response to a similar degree. The rank order of potencies for inhibition of both the sustained Ca++ response phase and (+)-[3H]SKF-10047 binding (Roman et al., J. Pharm. Pharmacol. 42: 439-440, 1989) were similar. These findings suggest that sigma 1 ligands indirectly modulate NMDA receptor complex function through sigma 1 receptors and that sigma ligands facilitate the desensitization of the Ca++ response to NMDA.
This article has been cited by other articles:
|
|
 |
|
  Y. Herrera, C. Katnik, J. D. Rodriguez, A. A. Hall, A. Willing, K. R. Pennypacker, and J. Cuevas {sigma}-1 Receptor Modulation of Acid-Sensing Ion Channel a (ASIC1a) and ASIC1a-Induced Ca2+ Influx in Rat Cortical Neurons J. Pharmacol. Exp. Ther., November 1, 2008; 327(2): 491 - 502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. T. Tchedre, R.-Q. Huang, A. Dibas, R. R. Krishnamoorthy, G. H. Dillon, and T. Yorio Sigma-1 Receptor Regulation of Voltage-Gated Calcium Channels Involves a Direct Interaction Invest. Ophthalmol. Vis. Sci., November 1, 2008; 49(11): 4993 - 5002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. T. Tchedre and T. Yorio {sigma}-1 Receptors Protect RGC-5 Cells from Apoptosis by Regulating Intracellular Calcium, Bax Levels, and Caspase-3 Activation Invest. Ophthalmol. Vis. Sci., June 1, 2008; 49(6): 2577 - 2588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Katnik, W. R. Guerrero, K. R. Pennypacker, Y. Herrera, and J. Cuevas Sigma-1 Receptor Activation Prevents Intracellular Calcium Dysregulation in Cortical Neurons during in Vitro Ischemia J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1355 - 1365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wang, A. R. Prescott, B. A. Spruce, J. Sanderson, and G. Duncan Sigma Receptor Antagonists Inhibit Human Lens Cell Growth and Induce Pigmentation Invest. Ophthalmol. Vis. Sci., April 1, 2005; 46(4): 1403 - 1408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hayashi and T.-P. Su Sigma-1 receptors at galactosylceramide-enriched lipid microdomains regulate oligodendrocyte differentiation PNAS, October 12, 2004; 101(41): 14949 - 14954. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. P. Monnet, M. P. Morin-Surun, J. Leger, and L. Combettes Protein Kinase C-Dependent Potentiation of Intracellular Calcium Influx by {sigma}1 Receptor Agonists in Rat Hippocampal Neurons J. Pharmacol. Exp. Ther., November 1, 2003; 307(2): 705 - 712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Mtchedlishvili and J. Kapur A Presynaptic Action of the Neurosteroid Pregnenolone Sulfate on GABAergic Synaptic Transmission Mol. Pharmacol., October 1, 2003; 64(4): 857 - 864. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zhang and J. Cuevas Sigma Receptors Inhibit High-Voltage-Activated Calcium Channels in Rat Sympathetic and Parasympathetic Neurons J Neurophysiol, June 1, 2002; 87(6): 2867 - 2879. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hayashi and T.-P. Su Regulating ankyrin dynamics: Roles of sigma-1 receptors PNAS, January 5, 2001; (2001) 21413698. [Abstract] [Full Text]
|
|
|
|
|
|
T. Hayashi, T. Maurice, and T.-P. Su Ca2+ Signaling via sigma 1-Receptors: Novel Regulatory Mechanism Affecting Intracellular Ca2+ Concentration J. Pharmacol. Exp. Ther., June 1, 2000; 293(3): 788 - 798. [Abstract] [Full Text]
|
|
|
|
|
|
O. Soriani, F. L. Foll, F. Roman, F. P. Monnet, H. Vaudry, and L. Cazin A-Current Down-Modulated by sigma Receptor in Frog Pituitary Melanotrope Cells Through a G Protein-Dependent Pathway J. Pharmacol. Exp. Ther., April 1, 1999; 289(1): 321 - 328. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Bhardwaj, M. Sawada, E. D. London, R. C. Koehler, R. J. Traystman, J. R. Kirsch, and F. M. Faraci Potent {varsigma}1-Receptor Ligand 4-Phenyl-1-(4-Phenylbutyl) Piperidine Modulates Basal and N-Methyl-D-Aspartate–Evoked Nitric Oxide Production In Vivo • Editorial Comment Stroke, November 1, 1998; 29(11): 2404 - 2411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Soriani, H. Vaudry, Y. A. Mei, F. Roman, and L. Cazin Sigma Ligands Stimulate the Electrical Activity of Frog Pituitary Melanotrope Cells through a G-Protein-Dependent Inhibition of Potassium Conductances J. Pharmacol. Exp. Ther., July 1, 1998; 286(1): 163 - 171. [Abstract] [Full Text]
|
|
|
|
|
|
E. R. Whittemore, V. I. Ilyin, and R. M. Woodward Antagonism of N-Methyl-D-Aspartate Receptors by sigma Site Ligands: Potency, Subtype-Selectivity and Mechanisms of Inhibition J. Pharmacol. Exp. Ther., July 1, 1997; 282(1): 326 - 338. [Abstract] [Full Text]
|
|
|
|
|
|
T. Hayashi and T.-P. Su Regulating ankyrin dynamics: Roles of sigma-1 receptors PNAS, January 16, 2001; 98(2): 491 - 496. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
