Differential effects of endogenous and synthetic cannabinoids on voltage-dependent calcium fluxes in rabbit T-tubule membranes: Comparison with fatty acids

Murat Oz, Yulia Tchugunova, Meral Dinc

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

The effects of cannabinoid receptor ligands including 2- arachidonoylglycerol, R-methanandamide, Δ 9-THC (Δ 9-tetrahydrocannabinol), WIN 55,212-2 [4,5-dihydro-2-methyl- 4(4-morpholinylmethyl)-1-(1-naphthalenylcarbonyl)-6H-pyrrolo[3,2,1ij] quinolin-6-one], CP 55,940 ([1alpha,2beta-(R)-5alpha]-(-)-5-(1,1-dimethyl)-2-[5- hydroxy-2-(3-hydroxypropyl) cyclohexyl-phenol]) and a series of fatty acids on depolarization-induced Ca 2+ effluxes mediated by voltage-dependent Ca 2+ channels were investigated comparatively in transverse tubule membrane vesicles from rabbit skeletal muscle. Vesicles were loaded with 45Ca 2+ and membrane potentials were generated by establishing potassium gradients across the vesicle using the ionophore valinomycin. Endocannabinoids, 2-arachidonoylglycerol and R-methanandamide (all 10 μM), inhibited depolarization-induced Ca 2+ effluxes and specific binding of [ 3H]PN 200-110 (isradipine) to transverse tubule membranes. On the other hand, synthetic cannabinoids, including CP 55,940, WIN 55,212-2, and Δ 9-THC (all 10 μM), were ineffective. Additional experiments using endocannabinoid metabolites suggested that whereas ethanolamine and glycerol were ineffective, arachidonic acid inhibited Ca 2+ effluxes and specific binding of [ 3H]PN 200-110. Further studies indicated that only those fatty acids containing two or more double bonds were effective in inhibiting depolarization-induced Ca 2+ effluxes and specific binding of [ 3H]PN 200-110. These results indicate that endocannabinoids, but not synthetic cannabinoids, directly inhibit the function of voltage-dependent calcium channels (VDCCs) and modulate the specific binding of calcium channel ligands of the dihydropyridine (DHP) class.

Original languageEnglish
Pages (from-to)47-58
Number of pages12
JournalEuropean Journal of Pharmacology
Volume502
Issue number1-2
DOIs
Publication statusPublished - Oct 11 2004

Keywords

  • Calcium channel
  • Cannabinoid
  • Endocannabinoid
  • Fatty acid
  • Skeletal muscle

ASJC Scopus subject areas

  • Pharmacology

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