title: Expression of epidermal N-methyl-D-aspartate receptors (NMDAR1) depends on formation of the granular layer--analysis in diseases with parakeratotic cornification.
abstract: Ionotrope glutamate receptors of the N-methyl-D-aspartate (NMDA) receptor type are expressed on keratinocytes and influence the intracellular calcium concentration. The importance of NMDA receptors in pathophysiological processes in the skin is, however, still unclear. Epidermal distribution patterns of NMDA receptors were investigated in dermatoses with parakeratotic cornification (psoriasis vulgaris and verrucae vulgares) and compared to the expression of filaggrin. The expression of NMDA receptors (R1 component) in paraffin-embedded normal epidermis (n = 22), psoriasis vulgaris (n = 21) and verrucae vulgares (n = 23) was examined and evaluated by means of digital image analysis. For quantitative characterization of the distribution patterns, a quotient was formed of the expression in the stratum granulosum and stratum basale ("NMDA ratio"). The distribution of NMDAR1 was compared to the immunohistochemical expression of filaggrin. Additionally the expression of filaggrin was investigated in HaCaT cells after treatment with the NMDA receptor antagonist MK-801. NMDA receptors were demonstrated in the epidermis of all preparations. In healthy skin, the highest receptor density was found in the stratum granulosum. This distribution pattern was basically also present in the dermatoses examined. Thus, the occurrence of parakeratosis in psoriasis vulgaris, but not in verrucae vulgares, was characterized by a significant reduction in the NMDA ratio (reduced expression of NMDAR1 in the upper epidermis). The immunohistochemical distribution of filaggrin was similar to that of NMDAR1. In HaCaT cells MK-801 suppressed the expression of filaggrin. NMDA receptors are expressed in human epidermis under physiological conditions especially in the stratum granulosum. Their reduced expression within parakeratotic epidermis in psoriasis vulgaris may be evidence of impaired intracellular calcium influx in this disease.
authors.affiliation: Department of Dermatology and Venerology, Martin-Luther-University Halle-Wittenberg, Ernst-Kromayer-Str. 5, 06097 Halle (Saale), Germany. matthias.fischer@medizin.uni-halle.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Fischer
authors.forename: Thomas
authors.initials: T
authors.lastname: William
authors.forename: Peter
authors.initials: P
authors.lastname: Helmbold
authors.forename: Johannes
authors.initials: J
authors.lastname: Wohlrab
authors.forename: Wolfgang Ch
authors.initials: WCh
authors.lastname: Marsch
mesh_terms: D002460:Cell Line; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004817:Epidermis / Q000378:metabolism*; D000091344:Filaggrin Proteins; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D010241:Parakeratosis / Q000378:metabolism*; D011565:Psoriasis / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012189:Retrospective Studies; D014018:Tissue Distribution; D014860:Warts / Q000378:metabolism*
chemical_list: D016291:Dizocilpine Maleate; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C000717249:FLG protein, human