Mechanisms of Psoralen Action in the Skin

The combination of psoralens and ultraviolet light (UVA, 320-400 nm), also referred to as PUVA, is a potent modulator of epidermal cell growth and differentiation. Although it has been postulated that PUVA exerts its actions by binding to DNA, our laboratory has obtained evidence that a specific, saturable, high-affinity receptor site independent of the DNA mediates the biologic actions of these drugs. This receptor is a 22,000 molecular weight protein present in membrane and cytoplasmic fractions of responsive cell types. Treatment of cells with psoralens followed by UV light causes activation of the receptor. This leads to specific cell surface membrane alterations, in particular phosphorylation of the receptor for epidermal growth factor (EGF). The EGF receptor is a transmembrane glycoprotein possessing intrinsic tyrosine kinase activity. Modification of the EGF receptor leads to a loss in its ability to bind EGF, as well as an inhibition of its tyrosine kinase activity. These data indicate that the psoralens act at the level of the cell membrane and that their biologic effects in the skin may be mediated by the ability of these drugs to disrupt normal growth factor functions.