γ-aminobutyric acid (GABA) induces a receptor-mediated reduction in GABA_A receptor α subunit messenger RNAs in embryonic chick neurons in culture

γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in brain, is known to interact with a subclass of receptors that activate a ligand-gated chloride ion channel. Exposure of cultured embryonic chick neurons to physiological concentrations of GABA results in a time-dependent down-regulation of these GABA_A receptors. To delineate the cellular mechanism(s) responsible for agonist-induced down-regulation of GABA_A receptors we quantified the levels of GABA_A receptor α subunit messenger RNAs, which encode the subunit(s) containing agonist recognition site(s), and observed a marked reduction in a subunit mRNAs following exposure of embryonic chick neurons to GABA. Both the down-regulation of GABA_A receptors and the reduction in α subunit mRNAs induced by GABA were completely antagonized by the specific GABA_A receptor antagonist SR-95531. These data demonstrate the presence of an agonist-induced receptor-mediated mechanism for regulating the expression of receptor subunit-encoding mRNAs that may be involved in the development of tolerance to the pharmacological actions of drugs known to act via GABA_A receptors.