{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T14:09:44Z","timestamp":1775052584545,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,10,23]],"date-time":"2012-10-23T00:00:00Z","timestamp":1350950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>3 adenosine receptor, <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>3<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>, belongs to the <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>i proteins coupled receptors. Activation of <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>3<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content> by its agonist, <jats:styled-content style=\"fixed-case\">IB<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MECA<\/jats:styled-content>, decreases c<jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content> and was expected to reduce melanin level. Unexpectedly, <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>16 melanoma cells exposed to <jats:styled-content style=\"fixed-case\">IB<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MECA<\/jats:styled-content> increased melanin levels in a dose\u2010dependent manner. Human skin explants exposed to <jats:styled-content style=\"fixed-case\">IB<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MECA<\/jats:styled-content> showed an increase in <jats:styled-content style=\"fixed-case\">DOPA<\/jats:styled-content> positive cells and in melanin deposition in keratinocytes. The agonist induced <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content> phosphorylation, leading to a rapid translocation of the transcription factor <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>i<jats:styled-content style=\"fixed-case\">TF<\/jats:styled-content> towards the nucleus. <jats:styled-content style=\"fixed-case\">DOPA<\/jats:styled-content> oxidase activity and melanin levels induced by <jats:styled-content style=\"fixed-case\">IB<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MECA<\/jats:styled-content> were further enhanced by <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>98509, an inhibitor <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content> signalling pathway. Our study shows that <jats:styled-content style=\"fixed-case\">IB<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MECA<\/jats:styled-content> decreases c<jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content> while inducing melanogenesis. The proposed mechanism involves activation of <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3<jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content> signalling pathway by \u03b2\/\u03b3 subunits of the <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content> protein coupled to <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>3<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>. The increase in melanin level in human skin explants suggests that <jats:styled-content style=\"fixed-case\">IB<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MECA<\/jats:styled-content> may be a potential candidate to the treatment of hypopigmentation of skin.<\/jats:p>","DOI":"10.1111\/exd.12028","type":"journal-article","created":{"date-parts":[[2012,9,17]],"date-time":"2012-09-17T12:31:44Z","timestamp":1347885104000},"page":"74-77","source":"Crossref","is-referenced-by-count":17,"title":["Enhancing pigmentation via activation of <scp>A<\/scp>3 adenosine receptors in <scp>B<\/scp>16 melanoma cells and in human skin explants"],"prefix":"10.1111","volume":"22","author":[{"given":"Lea","family":"Madi","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology School of Medicine Tel\u2010Aviv University Tel\u2010Aviv 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