• Bassil Hassan and Victor Ruiz-Velasco.
• Department of Anesthesiology, Penn State College of Medicine, Hershey, PA 17033, USA.
• Reg Anesth Pain Med. 2013 Jan 1; 38 (1): 21-7.

Background And Objectivesκ-Opioid receptor (κ-OR) activation is known to play a role in analgesia and central sedation. The purpose of the present study was to examine the effect of the κ-OR agonist, U-50488 (an arylacetamide), on Ca channel currents and the signaling proteins involved in acutely isolated rat dorsal root ganglion (DRG) neurons expressing the putative promoter region of the tetrodotoxin-resistant Na channel (NaV 1.8) that is known to be involved in pain transmission.MethodsAcutely isolated rat DRG neurons were transfected with cDNA coding for enhanced green fluorescent protein (EGFP), whose expression is driven by the NaV 1.8 promoter region. Thereafter, the whole-cell variant of the patch-clamp technique was used to record Ca channel currents in neurons expressing EGFP.ResultsExposure of EGFP-expressing DRG neurons to U-50488 (0.3-40 μM) led to voltage-independent inhibition of the Ca channel currents. The modulation of the Ca currents did not appear to be mediated by the Gα protein subfamilies: Gαi/o, Gαs, Gαq/11, Gα14, and Gαz. Furthermore, dialysis of the hydrolysis-resistant GDP analog, GDP-β-S (1 mM), did not affect the U-50488-mediated blocking effect, ruling out involvement of other G protein subunits. Finally, U-50488 (20 μM) blocked Ca channels heterologously expressed in HeLa cells that do not express κ-OR.ConclusionThese results suggest that the antinociceptive actions mediated by U-50488 are likely due to both a direct block of Ca channels in sensory neurons as well as G protein modulation of Ca currents via κ-OR-expressing neurons.

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