Competitive chrodrimanin B interactions with rat brain GABAA receptors revealed by radioligand binding assays

Abstract

Meroterpenoid compounds chrodrimanins produced by Talaromyces sp. YO-2 have been shown to act as competitive antagonists of silkworm larval GABA_A receptors using electrophysiology, yet no further evidence has been provided to support such an action. We have investigated the actions of chrodrimanin B on rat brain GABA_A receptors by binding assays with non-competitive ligand of GABA_A receptors [³H]EBOB and competitive ligands [³H]gabazine and [³H]muscimol. Chrodrimanin B did not significantly affect the binding of [³H]EBOB while reducing the binding of [³H]gabazine and [³H]muscimol to the rat membrane preparations. Chrodrimanin B increased the dissociation constant K_d of [³H]gabazine and [³H]muscimol without significantly affecting the maximum binding, pointing to competitive interactions of chrodrimanin B with rat GABA_A receptors in support of our previous observation that the compound acts as a competitive antagonist on the silkworm larval GABA receptor.

Keywords: Binding assay; Chrodrimanin B; EBOB; GABA(A) receptors; Gabazine; Muscimol.