Dexamethasone and forskolin synergistically increase [Met5]enkephalin accumulation in mixed brain cell cultures

M. K. McMillian, K. R. Pennypacker, L. Thai, G. C. Wu, H. H. Suh, K. L. Simmons, P. M. Hudson, S. B. Mullis Sawin, J. S. Hong

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9 Scopus citations


Possible synergistic effects of the glucocorticoid dexamethasone (DEX, 10-7 M) and the adenylate cyclase agonist forskolin (FSK, 10-5 M) on [Met5]enkephalin (ME) accumulation were examined in enriched rat glial cultures and in mixed neuronal/glial cultures. In enriched glial cultures, DEX and FSK each stimulated the accumulation of ME 2-3-fold over basal media levels, but there was little additional stimulation when these agonists were combined. In contrast, mixed neuronal/glial cultures showed only weak responses to DEX or ESK alone, but the combination of these agonists produced a pronounced synergistic effect on media ME accumulation (6-10-fold over basal levels). The DEX effect was mediated via a classical glucocorticoid receptor, since DEX was potent (acting over a concentration range of 10-11-10-7 M), mimicked by corticosterone (10-6 M), and blocked by the glucocorticoid receptor antagonist RU486. There was a pronounced time lag (2 days) for the synergistic effects of DEX + FSK to develop. In situ hybridization and immunocytochemical studies suggested that astrocytes were the major source for the increased ME production in all mixed neuronal/glial cultures examined. Creating a mixed culture by plating fetal neurons onto confluent, enriched P7 glial cultures inhibited accumulation of ME in the media. DEX + FSK, but neither agonist alone, overcame this neuronal inhibition and increased accumulation of media ME to levels identical to levels in stimulated enriched glial cultures. The net effect was a 6-fold increase in ME accumulation in the mixed neuronal/glial cultures relative to a 2.5-fold increase in the enriched glial cultures. Neuronal inhibition of basal glial ME production could explain the similar synergistic effects of DEX + FSK observed in all mixed neuronal/glial cultures examined, and may be important in suppressing ME production by astrocytes in the brain.

Original languageEnglish
Pages (from-to)67-74
Number of pages8
JournalBrain Research
Issue number1-2
StatePublished - Aug 19 1996


  • astrocyte
  • cyclic AMP
  • glia
  • glucocorticoid
  • neuron-glia interaction
  • opioid peptide
  • preproenkephalin

ASJC Scopus subject areas

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


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