Effects of WIN55,212-2 on voltage-gated sodium channels in trigeminal ganglion neurons of rats

Neurol Res. 2008 Feb;30(1):85-91. doi: 10.1179/016164107X228642.

Abstract

Objectives: This study was carried out to investigate the effects of WIN55,212-2, a potential cannabinoid receptor agonist, on voltage-gated sodium currents I(Na) in cultured trigeminal ganglion neurons of rats, and to investigate whether the anti-nociceptive effects of cannabinoid receptor subtype 1 (CB1) were produced through its modulation on I(Na).

Methods: Whole cell patch clamp techniques were used to record I(Na) before and after WIN55,212-2 was perfused in cultured trigeminal ganglion neurons of rats.

Results: WIN55,212-2 (0.01 micromol/l) could enhance I(Na) slightly by 11.5 +/- 4.7% (n=7, p<0.05), and this effect could not be blocked by AM251, the CB1 receptor antagonist. However, WIN55,212-2 could inhibit I(Na) in concentration dependent manner at concentrations from 0.1 to 100 micromol/l. The inhibitory rates were 17.4 +/- 6.0, 22.5 +/- 7.8, 43.9 +/- 9.4 and 73.9 +/- 6.7% respectively by 0.1, 1, 10, 100 micromol/l WIN55,212-2, and the EC(50) was 17.8 micromol/l (n=7, p<0.05 or p<0.01). This inhibitory effect could be blocked partly by 1 micromol/l AM251 (n=7, p<0.05). WIN55,212-2 (0.01 micromol/l) shifted the active curve of I(Na) leftward slightly (n=7, p<0.05), but had no effect on its stable inactive curve (n=7, p>0.05). WIN55,212-2 (10 micromol/l) did not affect the active and stable inactive curves of I(Na) (n=7, p>0.05).

Conclusion: WIN55,212-2 had bidirectional (two phases) effects on I(Na) in trigeminal ganglion neurons. It might act on different receptors, and the CB1 receptor participated in its modulation on I(Na).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoxazines / pharmacology*
  • Calcium Channel Blockers / pharmacology*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Drug Interactions
  • Electric Stimulation / methods
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / radiation effects
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Morpholines / pharmacology*
  • Naphthalenes / pharmacology*
  • Neurons / drug effects*
  • Patch-Clamp Techniques / methods
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Channels / physiology*
  • Trigeminal Ganglion / cytology*

Substances

  • Benzoxazines
  • Calcium Channel Blockers
  • Morpholines
  • Naphthalenes
  • Piperidines
  • Pyrazoles
  • Sodium Channels
  • AM 251
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone