High‐Affinity Cannabinoid Binding Site: Regulation by Ions, Ascorbic Acid, and Nucleotides

Jeffrey S. Nye, Adele M. Snowman, Susan Voglmaier, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review


Abstract: The high‐affinity cannabinoid site in rat brain is an integral component of brain membranes that recognizes cannabinoids with inhibitory constants (Ki) in the nanomolar range. To clarify its physiological role, we studied the regulation of [3H]5′‐trimethylammonium Δ8‐tetrahydrocannabinol ([3H]TMA) binding. The site is inhibited by heavy metal ions, such as La3+, at low micromolar concentrations; divalent cations, such as Ca2+ and Mg2+, inhibit [3H]TMA binding, though at somewhat higher concentrations. In contrast, [3H]TMA binding is stimulated by Fe2+, Cu2+, and Hg2+ ions. Ascorbic acid and its analogs are also stimulators of cannabinoid binding at low micromolar concentrations. Stimulation of [3H]TMA binding by ascorbate or ions is dependent upon molecular oxygen, but is not inhibited by metabolic poisons. Metabolically stable nucleoside triphosphate analogs enhance [3H]TMA binding by different mechanisms, with hydrolysis of a high‐energy phosphate bond apparently requisite for these influences. These results suggest that the cannabinoid binding site is associated with a nucleotide‐utilizing protein possessing multiple regulatory subsites.

Original languageEnglish (US)
Pages (from-to)1892-1897
Number of pages6
JournalJournal of Neurochemistry
Issue number6
StatePublished - Jun 1989


  • 5′‐Trimethylammonium Δ‐tetrahydrocannabinol
  • Ascorbic acid
  • Cannabinoids
  • Divalent cations
  • Heavy metal ions

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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