HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (15) Citing Articles via Google Scholar Google Scholar Articles by Spencer, J. D Articles by Schallreuter, K. U Search for Related Content PubMed PubMed Citation Articles by Spencer, J. D Articles by Schallreuter, K. U

¹ Clinical and Experimental Dermatology, Department of Biomedical Sciences, University of Bradford, Bradford BD7 1DP, UK
² Institute for Pigmentary Disorders in association with EM Arndt University Greifswald, Germany and University of Bradford, Bradford BD7 1DP, UK
³ Biomedical Sciences, University of Bradford, Bradford BD7 1DP, UK

(Requests for offprints should be addressed to K U Schallreuter; Email: K.Schallreuter{at}bradford.ac.uk)

The human skin holds the full machinery for pro-opiomelanocortin processing. The -melanocyte-stimulating hormone (-MSH)/melanocortin-1-receptor cascade has been implicated as a major player via the cAMP signal in the control of melanogenesis. Only very recently the ß-endorphin/µ-opiate receptor signal has been added to the list of regulators of melanocyte dendricity and melanin formation. In this context it was reported that (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (6BH₄) can act as an allosteric inhibitor of tyrosinase, the key enzyme in melanogenesis, and this inhibition is reversible by both - and ß-MSH. It was also shown earlier that 7BH₄, the isomer of 6BH₄, is twice as active in this inhibition reaction. However, as yet it is not known whether 7BH₄ is indeed present in loco in the melanosome. We here provide evidence that this isomer is present in this organelle in a concentration range up to 50 x 10^–6 M. Determination of ß-MSH in melanosomal extracts yielded 10 pg/mg protein. Moreover, we demonstrate reactivation of the 7BH₄/tyrosinase inhibitor complex by ß-MSH, whereas -MSH failed to do so. Furthermore, we show intra-melanosomal L-dopa formation from dopachrome by 7BH₄ in a concentration range up to 134 x 10^–6 M. Based on these results, we propose a new receptor-independent mechanism in the control of tyrosinase/melanogenesis by ß-MSH and the pterin 7BH₄.

This article has been cited by other articles:

				M. M. A. E. L. Salem, M. Shalbaf, N. C. J. Gibbons, B. Chavan, J. M. Thornton, and K. U. Schallreuter Enhanced DNA binding capacity on up-regulated epidermal wild-type p53 in vitiligo by H2O2-mediated oxidation: a possible repair mechanism for DNA damage FASEB J, November 1, 2009; 23(11): 3790 - 3807. [Abstract] [Full Text] [PDF]

				J. D. Spencer and K. U. Schallreuter Regulation of Pigmentation in Human Epidermal Melanocytes by Functional High-Affinity {beta}-Melanocyte-Stimulating Hormone/Melanocortin-4 Receptor Signaling Endocrinology, March 1, 2009; 150(3): 1250 - 1258. [Abstract] [Full Text] [PDF]

				A. L. Pey, A. Martinez, R. Charubala, D. J. Maitland, K. Teigen, A. Calvo, W. Pfleiderer, J. M. Wood, and K. U. Schallreuter Specific interaction of the diastereomers 7(R)- and 7(S)-tetrahydrobiopterin with phenylalanine hydroxylase: implications for understanding primapterinuria and vitiligo FASEB J, October 1, 2006; 20(12): 2130 - 2132. [Abstract] [Full Text] [PDF]