Abstract:The inhibitory glycine receptor (GlyR) is a member of the nicotinoid receptor superfamily. This heteropentameric Cl -channel is composed of different (1-4) and a -subunit and mediates fast synaptic transmission in the central nervous system. Since glycine, the natural ligand of GlyR has been found to enhance epidermal barrier recovery; we aimed at characterizing GlyR distribution in human skin and their function in skin physiology. We detected differentsubunits and the -GlyR subunit on mRNA and protein level in human skin and cultured keratinocytes and fibroblasts. In cultured human keratinocytes but not in fibroblasts, glycine induced proliferation. Epidermis-equivalents were significantly thicker than control if cultured in the presence of glycine. In human skin, GlyR immunoreactivity (IR) was detected in the upper epidermal layers. In eczema and psoriasis, GlyR IR was reduced in areas with parakeratosis suggesting a role of GlyR in terminal differentiation and epidermal barrier control.Keywords: Epidermal barrier, chloride, strychnine, amino acid, skin. INTROCUCTIONStructurally, glycine (aminoethanoic acid, C 2 H 5 NO 2 ) is the simplest of the 20 standard proteinogenic amino acids, and yet it has a number of important and distinct functions in the body [1]. In addition to its function as part of peptides and proteins, glycine is a major inhibitory neurotransmitter in adult spinal cord and brain stem, where it controls both motor and sensory pathways. After its release from the presynaptic terminals of glycinergic interneurons, glycine exerts multiple functions in the central nervous system, as an inhibitory neurotransmitter through activation of specific, Cl --permeable, ligand-gated ionotropic receptors (GlyR) and as an obligatory co-agonist with glutamate on the activation of N-methyl-D-aspartate (NMDA) receptors [2,3]. The hyperpolarizing action of glycine is selectively antagonized by strychnine, the most potent GlyR antagonist known [4].The GlyR of different species are composed of two glycosylated integral membrane proteins, the 1-4-subunit of 48 kDa and the -subunit of 58 kDa. In addition, in neuronal tissues, there is an associated peripheral membrane protein of 93 kDa named gephyrin [5][6][7]. The primary structures of GlyR -and -subunits deduced by molecular cloning show significant sequence and structural similarity to nicotinic acetylcholine receptor (nAChR), -aminobutyric acid type A (GABA A) receptor, and serotonin type 3 (5HT3) receptor proteins. In situ hybridization showed that the different GlyR subunit genes exhibit unique spatial and temporal expression patterns in spinal cord, brain stem, and some higher brain regions. GlyR 2-subunit transcripts predominate in the embryonic and neonatal brain and spinal cord, but are replaced Recently, several unexpected properties of glycine have been discovered. Like the structurally related nicotinic acetylcholine receptors [8], GlyR were shown to be expressed in peripheral, non-neuronal tissues and cells like macrophages and leukocytes sugge...