title: Release of tritiated agmatine from spinal synaptosomes.
abstract: Intrathecal agmatine (decarboxylated arginine) moderates induction of neuropathic pain, spinal cord injury, and opioid tolerance in rodents. An endogenous central nervous system molecule and N-methyl-D-aspartate receptor antagonist/nitric oxide synthase inhibitor, agmatine may be a neuromodulator. We evaluated depolarization-induced release of agmatine from purified spinal nerve terminals (synaptosomes). Agmatine immunoreactivity was observed colocalized or closely apposed to some synaptophysin- and/or synaptotagmin-labeled structures. A temperature- and concentration-dependent uptake of [3H]-agmatine into synaptosomes was observed, consistent with an uptake mechanism. Potassium-induced depolarization resulted in release of [3H]-agmatine from the synaptosomes in a Ca2+-dependent manner, consistent with a neuromodulatory function. These results agree with previous reports of agmatine uptake into synaptosomes of the brain and extend those results to include stimulated release and a spinal site of activity.
authors.affiliation: Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Cory J
authors.initials: CJ
authors.lastname: Goracke-Postle
authors.forename: Hoang Oanh X
authors.initials: HO
authors.lastname: Nguyen
authors.forename: Laura S
authors.initials: LS
authors.lastname: Stone
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Fairbanks
mesh_terms: D000376:Agmatine / Q000493:pharmacokinetics* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D026603:D-Aspartic Acid / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects; D016708:Synaptophysin / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D050857:Synaptotagmins / Q000378:metabolism; D013696:Temperature; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics*
chemical_list: D016708:Synaptophysin; D014316:Tritium; D050857:Synaptotagmins; D026603:D-Aspartic Acid; D011189:Potassium Chloride; D000376:Agmatine; D002118:Calcium