title: Spinal astrocytes produce and secrete dynorphin neuropeptides.
abstract: Dynorphin peptide neurotransmitters (neuropeptides) have been implicated in spinal pain processing based on the observations that intrathecal delivery of dynorphin results in proalgesic effects and disruption of extracellular dynorphin activity (by antisera) prevents injury evoked hyperalgesia. However, the cellular source of secreted spinal dynorphin has been unknown. For this reason, this study investigated the expression and secretion of dynorphin-related neuropeptides from spinal astrocytes (rat) in primary culture. Dynorphin A (1-17), dynorphin B, and α-neoendorphin were found to be present in the astrocytes, illustrated by immunofluorescence confocal microscopy, in a discrete punctate pattern of cellular localization. Measurement of astrocyte cellular levels of these dynorphins by radioimmunoassays confirmed the expression of these three dynorphin-related neuropeptides. Notably, BzATP (3'-O-(4-benzoyl)benzoyl adenosine 5'-triphosphate) and KLA (di[3-deoxy-D-manno-octulosonyl]-lipid A) activation of purinergic and toll-like receptors, respectively, resulted in stimulated secretion of dynorphins A and B. However, α-neoendorphin secretion was not affected by BzATP or KLA. These findings suggest that dynorphins A and B undergo regulated secretion from spinal astrocytes. These findings also suggest that spinal astrocytes may provide secreted dynorphins that participate in spinal pain processing.
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093-0744, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wahlert
authors.forename: Lydiane
authors.initials: L
authors.lastname: Funkelstein
authors.forename: Bethany
authors.initials: B
authors.lastname: Fitzsimmons
authors.forename: Tony
authors.initials: T
authors.lastname: Yaksh
authors.forename: Vivian
authors.initials: V
authors.lastname: Hook
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D004399:Dynorphins / Q000378:metabolism*; D004723:Endorphins / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D009479:Neuropeptides / Q000378:metabolism; D010146:Pain / Q000503:physiopathology; D011247:Pregnancy; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D058469:Receptors, Purinergic P2X / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D004723:Endorphins; D005904:Glial Fibrillary Acidic Protein; D009479:Neuropeptides; D011498:Protein Precursors; D058469:Receptors, Purinergic P2X; D051197:Toll-Like Receptor 4; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; C025681:alpha-neoendorphin; D004399:Dynorphins; C036200:rimorphin; D000255:Adenosine Triphosphate