Mechanisms for inhibition of P2 receptors signaling in neural cells

Fernando A. González, Gary A. Weisman, Laurie Erb, Cheikh I. Seye, Grace Y. Sun, Betty Velázquez, Melvin Hernández-Pérez, Nataliya E. Chorna

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Trophic factors are required to ensure neuronal viability and regeneration after neural injury. Although abundant information is available on the factors that cause the activation of astrocytes, little is known about the molecular mechanisms underlying the regulation of this process. Nucleotides released into the extracellular space from injured or dying neural cells can activate astrocytes via P2 nucleotide receptors. After a brief historical review and update of novel P2 receptor antagonists, this article focuses on recent advancements toward understanding molecular mechanisms that regulate G protein-coupled P2Y receptor signaling. Among P2Y receptor subtypes, the heptahelical P2Y2 nucleotide receptor interacts with vitronectin receptors via an RGD sequence in the first extracellular loop, and this interaction is required for effective signal transduction to activate mitogen-activated protein kinases ERK1/2, to mobilize intracellular calcium stores via activation of phospholipase C, protein kinase C isoforms, and to activate focal adhesion kinase and other signaling events. Ligation of vitronectin receptors with specific antibodies caused an inhibition of P2Y 2 receptor-induced ERK1/2 and p38 phosphorylation and P2Y2 receptor-induced cytoskeleton rearrangement and DNA synthesis. Structure-function studies have identified agonist-induced phosphorylation of the C-terminus of the P2Y2 receptor, an important mechanism for receptor desensitization. Understanding selective mechanisms for regulating P2Y2 receptor signaling could provide novel targets for therapeutic strategies in the management of brain injury, synaptogenesis, and neurological disorders.

Original languageEnglish (US)
Pages (from-to)65-79
Number of pages15
JournalMolecular Neurobiology
Volume31
Issue number1-3
StatePublished - Feb 2005
Externally publishedYes

Keywords

  • Antagonists
  • Astrocytes
  • Astrogliosis
  • Extracellular nucleotides
  • Nucleotide receptors
  • Purinergic signaling

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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  • Cite this

    González, F. A., Weisman, G. A., Erb, L., Seye, C. I., Sun, G. Y., Velázquez, B., Hernández-Pérez, M., & Chorna, N. E. (2005). Mechanisms for inhibition of P2 receptors signaling in neural cells. Molecular Neurobiology, 31(1-3), 65-79.