title: The influence of L-arginine on the regulation of epidermal arginase.
abstract: Topical preparations containing urea are firmly established in dermatological therapy and nursing care therapy. In addition, urea is frequently used as an inactive ingredient with disinfecting, keratoplastic and penetration-promoting action in topical preparations. Despite good tolerance and ensured action, particularly the irritating effect on erosive, exudative or strongly inflammatory skin restricts its application. Endogenic urea is synthesised from L-arginine by an extra-hepatic arginase in keratinocytes. This enzymatic reaction is subject to regulation by manganese ions and the intracellular L-arginine concentration. L-Arginine is predominantly transported into the cell by a membrane transport system that is dependent on the membrane potential. By incubating keratinocyte cultures in different concentrations of L-arginine and manganese chloride, it could be shown that the keratinocytic urea synthesis can be increased. In relevant concentrations, L-arginine and manganese chloride do not exhibit any proliferation-inhibiting action, do not trigger any apoptosis or necrosis, and are stable. An increase in the expression of arginase cannot be detected using L-arginine. The application of L-arginine alone or in combination with manganese chloride increases the endogenous intrakeratinocytic urea synthesis and thus offers an option for topical therapeutic application in cases of dry skin conditions.
authors.affiliation: Department of Dermatology and Venereology, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany. johannes.wohlrab@medizin.uni-halle.de
authors.forename: Johannes
authors.initials: J
authors.lastname: Wohlrab
authors.forename: Christina
authors.initials: C
authors.lastname: Siemes
authors.forename: Wolfgang C
authors.initials: WC
authors.lastname: Marsch
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001119:Arginase / Q000378:metabolism*; D001120:Arginine / Q000494:pharmacology / Q000502:physiology* / Q000633:toxicity; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D017895:Manganese Compounds; D009336:Necrosis; D015854:Up-Regulation; D014508:Urea / Q000378:metabolism
chemical_list: D002712:Chlorides; D017895:Manganese Compounds; D014508:Urea; D001120:Arginine; D001119:Arginase; C025340:manganese chloride