title: Effect of tumor necrosis factor-alpha on the reciprocal G-protein-induced regulation of norepinephrine release by the alpha2-adrenergic receptor.
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.
authors.affiliation: Department of Pathology and Anatomical Sciences, School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14214, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Reynolds
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Ignatowski
authors.forename: Robert N
authors.initials: RN
authors.lastname: Spengler
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001386:Azides / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D002462:Cell Membrane / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D010759:Phosphorus Isotopes / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001386:Azides; D010759:Phosphorus Isotopes; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D014409:Tumor Necrosis Factor-alpha; D010643:Phenoxybenzamine; D015016:Yohimbine; D000068438:Brimonidine Tartrate; C031907:GTP gamma-4-azidoanilide; D006160:Guanosine Triphosphate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D009638:Norepinephrine