Some indolic compounds as markers of the melanocyte activity.
The melanocyte activity was studied by analysis of the urinary excretion of indolic and cysteinyldopa compounds. One eumelanin marker, 5,6-dihydroxy-indole-2-carboxylic acid was identified and quantified in normal urine. However, its low concentration and sensitivity to oxidation made it less suitable for clinical studies. A methylated derivative of this substance, 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI-2-C), was also demonstrated in normal urine. A quantitative method was worked out and the normal urinary concentration of this substance was as high as the concentration of 5-S-cysteinyldopa. The concentrations of the eumelanic marker 6-hydroxy-5-methoxyindole-2-carboxylic acid and the pheomelanic marker 5-S-cysteinyldopa were determined in the urine of psoriasis patients during PUVA treatment and also in the urine of subjects with different skin colour. The melanocyte activity in albinotic patients and in albinotic mice was studied by the same technique. Some in vitro experiments were performed to show that 5-S-glutathionyldopa has the molecular properties of forming a mercapto-substituted indole derivative. The following main conclusions were drawn: 1. 5,6-Dihydroxyindole-2-carboxylic acid and 6-hydroxy-5-methoxyindole-2-carboxylic acid are both present in measurable amounts in normal urine. 2. The urinary concentration of 6-hydroxy-5-methoxyindole-2-carboxylic acid increased during PUVA treatment in a similar way as for 5-S-cysteinyldopa. 3. The eumelanic marker 6-hydroxy-5-methoxyindole-2-carboxylic acid was excreted in larger quantities by people with genetically dark skin, whereas the pheomelanic marker 5-S-cysteinyldopa was not related to pigment type. 4. In the urine of one albino patient and in the urine of albinotic mice a total absence of 6-hydroxy-5-methoxyindole-2-carboxylic acid was found. The urinary concentrations of 5-S-cysteinyldopa in these subjects were measurable but lower than in pigmented subjects. Thus, 6-hydroxy-5-methoxy-indole-2-carboxylic acid seems to be a more specific melanocyte marker than the cysteinyldopas.(ABSTRACT TRUNCATED AT 400 WORDS)
Hansson
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Department of Dermatology, University of Lund, Sweden.
D000417:Albinism / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000652:urine*; D003548:Cysteinyldopa / Q000031:analogs & derivatives / Q000378:metabolism / Q000652:urine; D006801:Humans; D007211:Indoles / Q000652:urine*; D008544:Melanocytes / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction; D011701:PUVA Therapy; D010858:Pigmentation
D015415:Biomarkers; D007211:Indoles; D003548:Cysteinyldopa; C017408:6-hydroxy-5-methoxy-2-indolylcarboxylic acid; C030692:5,6-dihydroxy-2-indolylcarboxylic acid; C033574:glutathionyldopa