Abstract:
:Alpha2-adrenergic receptors control norepinephrine (NE) release and tumor necrosis factor-alpha (TNF) production from neurons. TNF regulates NE release, depending on alpha2-adrenergic receptor functioning. The relationship between TNF production in the brain and alpha2-adrenergic receptor activation could have profound control over NE release. TNF and alpha2-adrenergic regulation of NE release was investigated in rat hippocampal slices incubated with pertussis toxin (PTX). The alpha2-adrenergic receptor couples to Galpha(i/o)-proteins to inhibit NE release; however, in slices preexposed to PTX, alpha2-adrenergic receptor activation facilitates NE release. TNF exposure subsequent to PTX restores alpha2-adrenergic inhibition of NE release. PTX exposure of hippocampal slices prevents agonist-induced increases in Galpha(i/o) labeling with a GTP analog; after subsequent TNF exposure, agonist-induced increases in Galpha(i/o) labeling are restored. TNF regulation of NE release transforms from inhibition to facilitation depending on alpha2-adrenergic receptor activation following PTX exposure. Therefore, TNF directs the coupling of the alpha2-adrenergic receptor, ultimately affecting NE release.
journal_name
J Neurosci Resjournal_title
Journal of neuroscience researchauthors
Reynolds JL,Ignatowski TA,Spengler RNdoi
10.1002/jnr.20407keywords:
subject
Has Abstractpub_date
2005-03-15 00:00:00pages
779-87issue
6eissn
0360-4012issn
1097-4547journal_volume
79pub_type
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