κ-Opioid receptor expression defines a phenotypically distinct subpopulation of astroglia: Relationship to Ca2+ mobilization, development, and the antiproliferative effect of opioids

Julie A. Gurwell, Marilyn J. Duncan, Katalin Maderspach, Anne Stiene-Martin, Robert P. Elde, Kurt F. Hauser

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

To assess the role of κ-opioid receptors in astrocyte development, the effect of κ-agonists on the growth of astroglia derived from 1-2-day-old mouse cerebra was examined in vitro. κ-Opioid receptor expression was assessed immunocytochemically (using KA8 and KOR1 antibodies), as well as functionally by examining the effect of κ-receptor activation on intracellular calcium ([Ca2+](i)) homeostasis and DNA synthesis. On days 6-7, as many as 50% of the astrocytes displayed κ-receptor (KA8) immunoreactivity or exhibited increases in [Ca2+](i) in response to κ-agonist treatment (U69,593 or U50,488H). Exposure to U69,593 (100 nM) for 72 h caused a significant reduction in number and proportion of glial fibrillary acidic protein-immunoreactive astrocytes incorporating bromodeoxyuridine (BrdU) that could be prevented by co-administering the κ-antagonist, nor-binaltorphimine (300 nM). In contrast, on day 14, only 5 or 14%, respectively, of the astrocytes were κ-opioid receptor (KA8) immunoreactive or displayed functional increases in [Ca2+](i). Furthermore, U69,593 (100 nM) treatment failed to inhibit BrdU incorporation at 9 days in vitro. Experimental manipulations showed that κ-receptor activation increases astroglial [Ca2+](i) both through influx via L-type channels and through mobilization of intracellular stores (which is an important Ca2+ signaling pathway in cell division). Collectively, these results indicate that a subpopulation of developing astrocytes express κ-opioid receptors in vitro, and suggest that the activation of κ-receptors mobilizes [Ca2+](i) and inhibits cell proliferation. Moreover, the proportion of astrocytes expressing κ-receptors was greatest during a period of rapid cell growth suggesting that they are preferentially expressed by proliferating astrocytes.

Original languageEnglish
Pages (from-to)175-187
Number of pages13
JournalBrain Research
Volume737
Issue number1-2
DOIs
StatePublished - Oct 21 1996

Bibliographical note

Funding Information:
The authors wish to thank Carol Turbek, Rong Zhou, Chrystal C. Godleske, and S. Eric Ryan for technical assistance. Supported by DA 06204 and Equipment Grants from NIDA, and by the Univ. Kentucky Medical Center.

Keywords

  • Cell division
  • Central nervous system maturation
  • Drug abuse
  • Endogenous opioid system
  • Fura-2
  • Intracellular calcium
  • Neuroglia
  • Nifedipine
  • Nor-binaltorphimine
  • Opioid receptor
  • Thapsigargin
  • U50488H
  • U69593

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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