γ-Aminobutyric acid (A) receptor agonists accelerate cutaneous barrier recovery and prevent epidermal hyperplasia induced by barrier disruption

Abstract

γ-Aminobutyric acid, is an amino acid transmitter, which mediates rapid inhibition in the central nervous system. γ-Aminobutyric acid (A) receptor is a ligand-gated chloride ion channel playing an important part in polarizing the cell membrane and reducing neuronal excitability in the neuron. In this study, we demonstrated the effects of γ-aminobutyric acid (A) receptor agonists on the cutaneous barrier repair process after the barrier disruption of hairless mice. Topical application of γ-aminobutyric acid and γ-aminobutyric acid (A) receptor-specific agonists, musimol and isoguvacine, after barrier disruption accelerated the barrier recovery. The γ-aminobutyric acid (B)-specific agonist, baclofen, did not affect the barrier recovery rate. The effect of γ-aminobutyric acid on the barrier recovery was blocked by the γ-aminobutyric acid (A)-receptor antagonist, bicuculline methobromide, but γ-aminobutyric acid (B) receptor antagonist, saclofen, did not affect the effect of γ-aminobutyric acid. Topical application of γ-aminobutyric acid also prevented epidermal hyperplasia, which was induced by the barrier insults under low environmental humidity and bicuculline methobromide blocked the effect of γ-aminobutyric acid on the epidermal hyperplasia. Immunoreactivity against γ-aminobutyric acid (A) polyclonal antibody was observed in hairless mouse epidermis. The fluorescent probe of γ-aminobutyric acid (A) receptor, TXR-musimol showed the localization of γ-aminobutyric acid (A) receptor in the epidermis of the hairless mice. Elevation of intracellular chloride ion was induced by γ-aminobutyric acid in cultured human keratinocytes and it was blocked by bicuculline methobromide. These results suggest that the γ-aminobutyric acid (A)-like receptor is associated with skin barrier homeostasis and regulation of the receptor clinically effective for barrier dysfunctional or epidermal hyperproliferative diseases.