High-affinity cannabinoid binding site: Regulation by ions, ascorbic acid, and nucleotides

J. S. Nye, Adele M Snowman, S. Voglmaier, Solomon H Snyder

Research output: Contribution to journalArticle

Abstract

The high-affinity cannabinoid site in rat brain is an integral component of brain membranes that recognizes cannabinoids with inhibitory constants (K(i)) 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
Volume52
Issue number6
StatePublished - 1989

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Cannabinoids
Ascorbic Acid
Nucleotides
Binding Sites
Ions
Brain
Heavy Ions
Dronabinol
Molecular oxygen
Poisons
Divalent Cations
Heavy Metals
Heavy ions
Nucleosides
Metal ions
Rats
Hydrolysis
Phosphates
Oxygen
Membranes

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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High-affinity cannabinoid binding site : Regulation by ions, ascorbic acid, and nucleotides. / Nye, J. S.; Snowman, Adele M; Voglmaier, S.; Snyder, Solomon H.

In: Journal of Neurochemistry, Vol. 52, No. 6, 1989, p. 1892-1897.

Research output: Contribution to journalArticle

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