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Br J Pharmacol. 2010 Oct;161(4):925-35. doi: 10.1111/j.1476-5381.2010.00935.x.

N-arachidonyl-glycine modulates synaptic transmission in superficial dorsal horn.

Author information

1
Pain Management Research Institute, Kolling Institute of Medical Research, Northern Clinical School, University of Sydney at Royal North Shore Hospital, NSW, Australia. jeong@med.usyd.edu.au

Abstract

BACKGROUND AND PURPOSE:

The arachidonyl-amino acid N-arachidonyl-glycine (NAGly) is an endogenous lipid, generated within the spinal cord and producing spinally mediated analgesia via non-cannabinoid mechanisms. In this study we examined the actions of NAGly on neurons within the superficial dorsal horn, a key site for the actions of many analgesic agents.

EXPERIMENTAL APPROACH:

Whole cell patch clamp recordings were made from lamina II neurons in rat spinal cord slices to examine the effect of NAGly on glycinergic and NMDA-mediated synaptic transmission.

KEY RESULTS:

N-arachidonyl-glycine prolonged the decay of glycine, but not β-alanine induced inward currents and decreased the amplitude of currents induced by both glycine and β-alanine. NAGly and ALX-1393 (inhibitor of the glycine transporter, GLYT2), but not the GLYT1 inhibitor, ALX-5407, produced a strychnine-sensitive inward current. ALX-5407 and ALX-1393, but not NAGly prolonged the decay phase of glycine receptor-mediated miniature inhibitory postsynaptic currents (IPSCs). NAGly prolonged the decay phase of evoked IPSCs, although to a lesser extent than ALX-5407 and ALX-1393. In the presence of ALX-1393, NAGly shortened the decay phase of evoked IPSCs. ALX-5407 increased and NAGly decreased the amplitude of evoked NMDA-mediated excitatory postsynaptic currents.

CONCLUSIONS AND IMPLICATIONS:

Our results suggest that NAGly enhanced inhibitory glycinergic synaptic transmission within the superficial dorsal horn by blocking glycine uptake via GLYT2. In addition, NAGly decreased excitatory NMDA-mediated synaptic transmission. Together, these findings provide a cellular explanation for the spinal analgesic actions of NAGly.

PMID:
20860669
PMCID:
PMC2992905
DOI:
10.1111/j.1476-5381.2010.00935.x
[Indexed for MEDLINE]
Free PMC Article

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