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.