gamma-Aminobutyric acid, is an
amino acid transmitter, which mediates rapid inhibition in the central nervous system.
gamma-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
gamma-aminobutyric acid (A) receptor agonists on the cutaneous barrier repair process after the barrier disruption of hairless mice. Topical application of
gamma-aminobutyric acid and
gamma-aminobutyric acid (A) receptor-specific agonists, musimol and
isoguvacine, after barrier disruption accelerated the barrier recovery. The
gamma-aminobutyric acid (B)-specific agonist,
baclofen, did not affect the barrier recovery rate. The effect of
gamma-aminobutyric acid on the barrier recovery was blocked by the
gamma-aminobutyric acid (A)-receptor antagonist,
bicuculline methobromide, but
gamma-aminobutyric acid (B) receptor antagonist,
saclofen, did not affect the effect of
gamma-aminobutyric acid. Topical application of
gamma-aminobutyric acid also prevented epidermal
hyperplasia, which was induced by the barrier insults under low environmental humidity and
bicuculline methobromide blocked the effect of
gamma-aminobutyric acid on the epidermal
hyperplasia. Immunoreactivity against
gamma-aminobutyric acid (A) polyclonal antibody was observed in hairless mouse epidermis. The
fluorescent probe of
gamma-aminobutyric acid (A) receptor, TXR-musimol showed the localization of
gamma-aminobutyric acid (A) receptor in the epidermis of the hairless mice. Elevation of intracellular
chloride ion was induced by
gamma-aminobutyric acid in cultured human keratinocytes and it was blocked by
bicuculline methobromide. These results suggest that the
gamma-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.