Abstract
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 language | English |
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Pages (from-to) | 67-74 |
Number of pages | 8 |
Journal | Brain Research |
Volume | 730 |
Issue number | 1-2 |
DOIs | |
State | Published - Aug 19 1996 |
Keywords
- astrocyte
- cyclic AMP
- glia
- glucocorticoid
- neuron-glia interaction
- opioid peptide
- preproenkephalin
ASJC Scopus subject areas
- General Neuroscience
- Molecular Biology
- Clinical Neurology
- Developmental Biology