Phenotypical and Molecular Profiling of the Extraneuronal Cholinergic System of the Skin

Abstract

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, alpha3, alpha5, beta2, and beta4 were expressed in the basal cell layer (BCL) and in a single cell layer in the stratum granulosum; alpha9 was expressed in the basal and lower spinous layers. alpha7, alpha10, and beta1 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 alpha9, beta1, and m4 were found in the BCL whereas the alpha9, m4, and m5 ACh-R were restricted to the central cell layer. The alpha5, beta1, beta2, m1-m4 chains were strongly expressed in the inner root sheath. Undifferentiated sebocytes expressed the alpha3, alpha9, beta4, m3-m5 ACh-R whereas alpha7, beta2, beta4, m2, and m4 were found in mature sebocytes. In sweat glands, the alpha3*, alpha7, and m2-m5 ACh-R were most prominent in the myoepithelial cells whereas alpha9, beta2, 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.

Molecular Interaction of α-Conotoxin RgIA with the Rat α9α10 Nicotinic Acetylcholine Receptor

“…In addition to the auditory system, transcripts and/or protein for a9 and a10 subunits have been found in lymphocytes, skin keratinocytes, sperm, dorsal root ganglion, sympathetic neurons, macrophages, and adrenal chromaffin cells (Nguyen et al, 2000;Lustig et al, 2001;Lips et al, 2002;Haberberger et al, 2004;Kurzen et al, 2004;Peng et al, 2004;Kumar and Meizel, 2005;Colomer et al, 2010;Simard et al, 2013). The physiologic role of a9a10 nAChRs in the auditory system has been determined through studies done with a9 and a10 knockout mice (Vetter et al, 1999(Vetter et al, , 2007.…”

Identification and Functional Characterization of the Muscarinic Receptor M3 in the Human Keratinocyte Cell Line HaCaT

“…Interestingly, in human epidermis the subtypes M3 and M5 were predominantly identifi ed in the basal cell layer by immunohistochemistry [Ndoye et al, 1998;Kurzen et al, 2004]. Immunoreactivity against subtypes M1 and M4 was additionally observed in the upper more differentiated layers.…”

Neuronal nicotinic acetylcholine receptor expression and function on nonneuronal cells

“…53 Grando and colleagues 98 established that KCs express nAChRs and that these receptors respond functionally to nicotine. Kurzen et al 99 localized nAChR subunit expression in the skin and conclude that there is a very distinctive pattern of subunit expression in normal human epidermis. Perhaps more important than issues pertaining to premature wrinkling is the relationship between smoking (and nicotine use) and delayed wound healing.…”