High affinity binding of corticosterone to mammalian neuronal membranes: Possible role of corticosteroid binding globulin

Miles Orchinik, Nicholas Hastings, Diane Witt, Bruce S. McEwen

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

The signal transduction mechanisms mediating rapid steroid actions are poorly understood. To characterize corticosteroid interaction with neuronal membranes in a species with rapid behavioral responses to corticosterone, we examined [3H]corticosterone binding to membranes prepared from prairie vole brains. At 22°C, the rates of association and dissociation of [3H]corticosterone with well-washed synaptosomal membranes were very rapid. Specific binding was characterized by high affinity (K(d) = 6.01 nM) and low density (B(max) = 63.1 fmol/mg protein). The binding sites were highly specific for naturally occurring glucocorticoids and the density of binding sites appeared to vary by neuroanatomical region. Unlike most G-protein-coupled receptors, the high-affinity binding of [3H]corticosterone to vole brain membranes was unaffected by the addition of Mg2+ or guanyl nucleotides. Surprisingly, saline perfusion of vole brains before tissue homogenization greatly reduced high-affinity binding. In addition, the affinity and specificity of corticosteroid binding sites were similar in vole neuronal membranes and vole plasma. These data suggest that corticosteroid binding globulins may facilitate [3H]corticosterone binding to neuronal membranes. However, the addition of blood to perfused brains before homogenization did not restore high-affinity binding, so the role of plasma binding globulins is unclear. Whether these binding phenomena represent a technical artifact or a regulatory mechanism for corticosteroid action has yet to be determined.

Original languageEnglish (US)
Pages (from-to)229-236
Number of pages8
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume60
Issue number3-4
DOIs
StatePublished - Feb 1997

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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