Ultrastructural localization and differentiation of membrane-bound ATP utilizing enzymes including adenyl cyclase in normal and psoriatic epidermis*

Abstract

The total membrane-bound ATP hydrolytic activity in human epidermis is due to the activities of at least three differently located enzymes, namely Mg++-activated ATPase, phosphomonoesterase and adenyl cyclase. Cytochemical studies on psoriatic epidermis with various inhibitory and stimulatory substances showed reduced activities of ATPase and phosphomonoesterase, and a lack of sensitivity of adenyl cyclase to specific stimulators such as isoproterenol and glucagon. Since no differences of basal adenyl cyclase activity were observed between normal and psoriatic human skin without stimulation, it seems likely that in psoriasis a latent defect of adenyl cyclase may exist, resulting in a deficient response of this enzyme to regulatory agents. In conclusion, the present study reveals that not a single enzyme but the entire membrane-bound nucleotide metabolism is altered in psoriatic keratinocytes, causing a disturbance of the membrane-bound energy utilization, similar to findings in proliferating tumour cells.

Purinergic Signaling in Healthy and Diseased Skin

“…''Adenosine increased cAMP levels in lesioned and uninvolved areas of epidermis obtained from psoriasis patients'' (Duell, 1980). A defective purine nucleotide synthetic pathway has been described in psoriasis patients (Kiehl and Ionescu, 1992) and nucleotide metabolism is altered in psoriatic keratinocytes (Mahrle and Orfanos, 1975). The ability to incorporate [H 3 ]adenine into ATP and adenyl cyclase activity was significantly lower in psoriasis plaques than in uninvolved skin and lower than in normal skin of control subjects (Mui et al, 1975).…”

Erythrocyte membrane phosphorylation in untreated and in etretinate-treated psoriatic patients*

“…Alterations in the cyclic nucleotide system (Voorhees et al, 1974)3 in membrane-bound ATPase and phosphomonoesterase activities (Mahrle & Orfanos, 1975)3 in membrane-associated hydrolases (Mier & Van den Hurk, 1976), in several lipid components such as cholesterol and phospholipids (Gara et al, 1964;Tsambaos & Mahrle, 1979)) and in uptake of labelled sugars into cell membrane (Roelfzema et al, 1981), strongly suggest that aberrations of membranemediated growth control mechanisms may be relevant to the expression of psoriasis (Mahrle & Orfanos, 1977). In a previous communication (Kumar et al, 1983), we reported that psoriatic patients exhibit decreased phosphorylation of red cell membrane polypeptides suggesting that membrane alterations may be part of a basic defect in psoriasis that may involve tissues other than skin.…”

New Concepts in the Pathogenesis of Psoriasis

“…Functional abnormalities of membrane-bound enzymes in psoriasis are not limited to the disturbance of adenyl cyclase (Wright et al, 1973) but include a decrease of ATPase and acid phosphoesterase activities (Mahrle & Orfanos, 1974;Mahrle& Orfanos, 1975).…”