| 17227436 |
Goracke-Postle CJ, Overland AC, Stone LS, Fairbanks CA: Agmatine transport into spinal nerve terminals is modulated by polyamine analogs. J Neurochem. 2007 Jan;100(1):132-41.
Agmatine (decarboxylated arginine) is an endogenous amine found in the CNS that antagonizes NMDA receptors and inhibits nitric oxide synthase. Intrathecally administered agmatine inhibits hyperalgesia evoked by inflammation, nerve injury and intrathecally administered NMDA. These actions suggest an antiglutamatergic neuromodulatory role for agmatine in the spinal cord. Such a function would require a mechanism of regulated clearance of agmatine such as neuronal or glial uptake. Consistent with this concept, radiolabeled agmatine has been shown to accumulate in synaptosomes, but the mechanism of this transport has not been fully characterized. The present study describes an agmatine uptake system in spinal synaptosomes that appears driven by a polyamine transporter. [(3) H] Agmatine uptake was Ca (2+), energy and temperature dependent. [(3) H] Agmatine transport was not moderated by L-arginine, L-glutamate, glycine, GABA, norepinephrine or serotonin. In contrast, [(3) H] agmatine uptake was concentration dependently inhibited by unlabeled putrescine and by unlabeled spermidine (at significantly higher concentrations). Similarly, [(3) H] putrescine uptake was inhibited in a concentration-dependent manner by unlabeled agmatine and spermidine. The polyamine analogs paraquat and methylglyoxal bis (guanylhydrazone) inhibited, whereas the polyamine transport enhancer difluoromethylornithine increased, [(3) H] agmatine transport. Taken together, these results suggest that agmatine transport into spinal synaptosomes may be governed by a polyamine transport mechanism. |
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