title: gamma-Aminobutyric acid (A) receptor agonists accelerate cutaneous barrier recovery and prevent epidermal hyperplasia induced by barrier disruption.
abstract: 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.
authors.affiliation: Shiseido Research Center, Fukuura, Kanazawa-ku, Yokohama, Japan. mitsuhiro.denda@to.shiseido.co.jp
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Denda
authors.forename: Kaori
authors.initials: K
authors.lastname: Inoue
authors.forename: Shinji
authors.initials: S
authors.lastname: Inomata
authors.forename: Sumiko
authors.initials: S
authors.lastname: Denda
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D018755:GABA Agonists / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D006813:Humidity; D006965:Hyperplasia / Q000517:prevention & control; D007539:Isonicotinic Acids / Q000494:pharmacology; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D009118:Muscimol / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D007539:Isonicotinic Acids; D011963:Receptors, GABA-A; D009118:Muscimol; D001418:Baclofen; C015300:isoguvacine