Selective potentiation of alpha 1 glycine receptors by ginkgolic acid.

ABSTRACT: Glycine receptors (GlyRs) belong to the superfamily of pentameric cys-loop receptor-operated channels and are involved in numerous physiological functions, including movement, vision, and pain. In search for compounds performing subunit-specific modulation of GlyRs we studied action of ginkgolic acid, an abundant Ginkgo biloba product. Using patch-clamp recordings, we analyzed the effects of ginkgolic acid in concentrations from 30 nM to 25 ?M on ?1-?3 and ?1/?, ?2/? configurations of GlyR and on GABAARs expressed in cultured CHO-K1 cells and mouse neuroblastoma (N2a) cells. Ginkgolic acid caused an increase in the amplitude of currents mediated by homomeric ?1 and heteromeric ?1/? GlyRs and provoked a left-shift of the concentration-dependent curves for glycine. Even at high concentrations (10-25 ?M) ginkgolic acid was not able to augment ionic currents mediated by ?2, ?2/?, and ?3 GlyRs, or by GABAAR consisting of ?1/?2/?2 subunits. Mutation of three residues (T59A/A261G/A303S) in the ?2 GlyR subunit to the corresponding ones from the ?1 converted the action of ginkgolic acid to potentiation with a distinct decrease in EC50 for glycine, suggesting an important role for these residues in modulation by ginkgolic acid. Our results suggest that ginkgolic acid is a novel selective enhancer of ?1 GlyRs.

SUBMITTER: Maleeva G 

PROVIDER: S-EPMC4624854 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature