Release of tritiated agmatine from spinal synaptosomes.
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.
Goracke-Postle
Cory J
CJ
Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Nguyen
Hoang Oanh X
HO
Stone
Laura S
LS
Fairbanks
Carolyn A
CA
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*
D016708:Synaptophysin; D014316:Tritium; D050857:Synaptotagmins; D026603:D-Aspartic Acid; D011189:Potassium Chloride; D000376:Agmatine; D002118:Calcium