Phenotypical and molecular profiling of the extraneuronal cholinergic system of the skin

We present molecular and protein profiling of all acetylcholine receptors (ACh-R) in human scalp skin using PCR, in situ hybridization and double-labeling immunofluorescence. Within the epidermis, the nicotinic (n)ACh-R subunits, α3, α5, β2, and β4 were expressed in the basal cell layer (BCL) and in a single cell layer in the stratum granulosum; α9 was expressed in the basal and lower spinous layers. α7, α10, and β1 were preferentially detected in the upper spinous and granular layers. Of the muscarinic (m)ACh-R, m1 and m4 were found in the suprabasal layers, whereas m2, m3, and m5 remained restricted to the lower layers. In the outer root sheath of the hair follicle, all ACh-R except α9, β1, and m4 were found in the BCL whereas the α9, m4, and m5 ACh-R were restricted to the central cell layer. The α5, β1, β2, m1-m4 chains were strongly expressed in the inner root sheath. Undifferentiated sebocytes expressed the α3, α9, β4, m3-m5 ACh-R whereas α7, β2, β4, m2, and m4 were found in mature sebocytes. In sweat glands, the α3*, α7, and m2-m5 ACh-R were most prominent in the myoepithelial cells whereas α9, β2, m1, m3, and m4 ACh-R were present in the acinar cells. Taken together, our data result in a complete molecular map of the extraneuronal cholinergic system of the skin that may be translated into distinct functional reaction patterns.