Mitogenic signaling from P1 and P2 purinergic receptors to mitogen- activated protein kinase in human fetal astrocyte cultures

Joseph T. Neary, Micheline McCarthy, Yuan Kang, Sylvia Zuniga

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

To investigate potential trophic actions of extracellular ATP in human astrocytes, we have examined mitogenic signaling by purinergic receptors in cultures prepared from first trimester rostral central nervous system tissue. We found that ATP and ATPγS, a hydrolysis-resistant analog, stimulated DNA synthesis, thereby indicating that P2 purinergic receptors can stimulate mitogenic signaling in these cells. In addition, ATP activated a mitogen- activated protein kinase (MAPK) termed ERK (extracellular signal-regulated protein kinase), a key component of signal tranSduction pathways involved in cellular proliferation and differentiation. The activation of MAPK was mediated at least in part by P2 purinergic receptors, because a P2 purinoceptor antagonist, suramin, inhibited the ATP-evoked stimulation by 50%, whereas a P1 purinergic-receptor antagonist, 8-(para-sulfonphenyl)- theophylline; was without effect. In contrast to rat astrocytes, adenosine/P1 purinergic-receptor agonists, 2-chloroadenosine and 5'-N- ethylcarboxyamidoadenosine, stimulated MAPK activity and DNA synthesis in human astrocytes. A selective inhibitor of protein kinase C, Ro 31-8220, blocked the ability of ATP and adenosine analogs to stimulate MAPK, thereby indicating that protein kinase C is upstream of MAPK in both P2- and P1- receptor signaling pathways. An inhibitor of the MAPK activator MEK, PD 098059, effectively blocked ATP- and 2-chloroadenosine-induced DNA synthesis, thereby indicating that the ERK/MAPK cascade mediates mitogenic signaling by P2 and P1 purinergic receptors in human fetal astrocytes. These findings suggest a role for P1 and P2 purinergic receptors in the proliferation of human fetal astrocytes.

Original languageEnglish (US)
Pages (from-to)159-162
Number of pages4
JournalNeuroscience Letters
Volume242
Issue number3
DOIs
StatePublished - Feb 20 1998

Keywords

  • Extracellular signal-regulated protein kinase
  • Human astrocytes
  • Mitogen-activated protein kinase
  • Proliferation
  • Purinergic receptor

ASJC Scopus subject areas

  • Neuroscience(all)

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