QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (39) Citing Articles via Google Scholar Google Scholar Articles by Dubin, A. E. Articles by Chun, J. Search for Related Content PubMed PubMed Citation Articles by Dubin, A. E. Articles by Chun, J.

 Previous Article  |  Next Article 

The Journal of Neuroscience, February 15, 1999, 19(4):1371-1381

Lysophosphatidic Acid Stimulates Neurotransmitter-Like Conductance Changes that Precede GABA and L-Glutamate in Early, Presumptive Cortical Neuroblasts

Adrienne E. Dubin^{1, 2}, Tristram Bahnson^{1, 2}, Joshua A. Weiner^{1, 3}, Nobuyuki Fukushima¹, and Jerold Chun^{1, 4}

¹ The Department of Pharmacology, ² The Department of Medicine, ³ Neurosciences Graduate Program, and ⁴ Neurosciences and Biomedical Sciences Graduate Programs, School of Medicine, University of California, San Diego, California 92093-0636

During neurogenesis in the embryonic cerebral cortex, the classical neurotransmitters GABA and L-glutamate stimulate ionic conductance changes in ventricular zone (VZ) neuroblasts. Lysophosphatidic acid (LPA) is a bioactive phospholipid producing myriad effects on cells including alterations in membrane conductances (for review, see ). Developmental expression patterns of its first cloned receptor gene, lp_A1/vzg-1 (; ) in the VZ suggested that functional LPA receptors were synthesized at these early times, and thus, LPA could be an earlier stimulus to VZ cells than the neurotransmitters GABA and L-glutamate. To address this possibility, primary cultures of electrically coupled, presumptive cortical neuroblast clusters were identified by age, morphology, electrophysiological profile, BrdU incorporation, and nestin immunostaining. Single cells from cortical neuroblast cell lines were also examined. Whole-cell variation of the patch-clamp technique was used to record from nestin-immunoreactive cells after stimulation by local administration of ligands. After initial plating at embryonic day 11 (E11), cells responded only to LPA but not to GABA or L-glutamate. Continued growth in culture for up to 12 hr produced more LPA-responsive cells, but also a growing population of GABA- or L-glutamate-responsive cells. Cultures from E12 embryos showed LPA as well as GABA and L-glutamate responses, with LPA-responsive cells still representing a majority. Overall, >50% of cells responded to LPA with depolarization mediated by either chloride or nonselective cation conductances. These data implicate LPA as the earliest reported extracellular stimulus of ionic conductance changes for cortical neuroblasts and provide evidence for LPA as a novel, physiological component in CNS development.

Key words: lysophosphatidic acid; LPA; chloride currents; cation currents; cerebral cortex; embryonic development; lysophospholipids; programmed cell death

---

Copyright © 1999 Society for Neuroscience  0270-6474/99/1941371-11$05.00/0

This article has been cited by other articles:

				G. Estivill-Torrus, P. Llebrez-Zayas, E. Matas-Rico, L. Santin, C. Pedraza, I. De Diego, I. Del Arco, P. Fernandez-Llebrez, J. Chun, and F. R. De Fonseca Absence of LPA1 Signaling Results in Defective Cortical Development Cereb Cortex, April 1, 2008; 18(4): 938 - 950. [Abstract] [Full Text] [PDF]

				C.-W. Lee, R. Rivera, A. E. Dubin, and J. Chun LPA4/GPR23 Is a Lysophosphatidic Acid (LPA) Receptor Utilizing Gs-, Gq/Gi-mediated Calcium Signaling and G12/13-mediated Rho Activation J. Biol. Chem., February 16, 2007; 282(7): 4310 - 4317. [Abstract] [Full Text] [PDF]

				C.-W. Lee, R. Rivera, S. Gardell, A. E. Dubin, and J. Chun GPR92 as a New G12/13- and Gq-coupled Lysophosphatidic Acid Receptor That Increases cAMP, LPA5 J. Biol. Chem., August 18, 2006; 281(33): 23589 - 23597. [Abstract] [Full Text] [PDF]

				D. S. Henshel Control of Glutathione Synthesis in Early Embryo Development Toxicol. Sci., October 1, 2004; 81(2): 257 - 259. [Full Text] [PDF]

				S. R. Chaplan, H.-Q. Guo, D. H. Lee, L. Luo, C. Liu, C. Kuei, A. A. Velumian, M. P. Butler, S. M. Brown, and A. E. Dubin Neuronal Hyperpolarization-Activated Pacemaker Channels Drive Neuropathic Pain J. Neurosci., February 15, 2003; 23(4): 1169 - 1178. [Abstract] [Full Text] [PDF]

				J. J. A. Contos, I. Ishii, and J. Chun Lysophosphatidic Acid Receptors Mol. Pharmacol., April 13, 2001; 58(6): 1188 - 1196. [Abstract] [Full Text]

				J. J. A. Contos, N. Fukushima, J. A. Weiner, D. Kaushal, and J. Chun Requirement for the lpA1 lysophosphatidic acid receptor gene in normal suckling behavior PNAS, November 21, 2000; 97(24): 13384 - 13389. [Abstract] [Full Text] [PDF]

				A. E. Dubin, R. Huvar, M. R. D'Andrea, J. Pyati, J. Y. Zhu, K. C. Joy, S. J. Wilson, J. E. Galindo, C. A. Glass, L. Luo, et al. The Pharmacological and Functional Characteristics of the Serotonin 5-HT3A Receptor Are Specifically Modified by a 5-HT3B Receptor Subunit J. Biol. Chem., October 22, 1999; 274(43): 30799 - 30810. [Abstract] [Full Text] [PDF]

				J. A. Weiner and J. Chun Schwann cell survival mediated by the signaling phospholipid lysophosphatidic acid PNAS, April 27, 1999; 96(9): 5233 - 5238. [Abstract] [Full Text] [PDF]

				T. Moller, J. J. Contos, D. B. Musante, J. Chun, and B. R. Ransom Expression and Function of Lysophosphatidic Acid Receptors in Cultured Rodent Microglial Cells J. Biol. Chem., July 6, 2001; 276(28): 25946 - 25952. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help