title: Alteration of tyrosinase activity in human melanocytes and melanoma cells by histamine H2 and H3 ligands.
abstract: Nontoxic doses of the histamine H2 antagonists ranitidine, cimetidine, lamtidine and mifentidine rapidly and reversibly increased tyrosinase activity in an amelanotic human melanoma cell line (MM96L) with low constitutive activity. The H2 antagonists, famotidine and MGTI, and the imidazol(in)e receptor ligand clonidine had no effect either alone or in competition with ranitidine, whilst metiamide decreased tyrosinase activity. Lysosomotropic amines had a similar effect to ranitidine, except that induction reached a plateau at 6 h and was insensitive to amiloride. Human melanocytes and pigmented human melanoma cell lines exhibited minimal levels of tyrosinase induction, which was dependent on protein synthesis but not on RNA or DNA synthesis. Constitutive tyrosinase activity in MM96L cells was much less stable than in melanocytes and pigmented melanoma cells. No change was observed in expression of gp75, neural specific octamer binding proteins, or in mRNA levels of tyrosinase, Pmel-17 and gp75 (TRP-1). Tyrosinase was inhibited by the H3 agonist imetit but not by alpha-methylhistamine or the H3 antagonist thioperamide. Overall, this work showed that certain H2 antagonists activate an unstable form of tyrosinase in amelanotic melanoma cells by a post-transcriptional mechanism dependent on protein synthesis. An imidazoline/guanidinium receptor site rather than the H2 receptor appeared to be involved.
authors.affiliation: Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, Herston, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Le Gros
authors.forename: X M
authors.initials: XM
authors.lastname: Zhang
authors.forename: P G
authors.initials: PG
authors.lastname: Parsons
mesh_terms: D001932:Brain Neoplasms / Q000556:secondary; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004790:Enzyme Induction; D017442:Histamine Agonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008544:Melanocytes / Q000187:drug effects* / Q000201:enzymology*; D018328:Melanoma, Amelanotic / Q000188:drug therapy* / Q000201:enzymology* / Q000556:secondary; D014442:Monophenol Monooxygenase / Q000096:biosynthesis / Q000187:drug effects* / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D011899:Ranitidine / Q000494:pharmacology; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000187:drug effects* / Q000378:metabolism*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000201:enzymology; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D017442:Histamine Agonists; D006635:Histamine H2 Antagonists; D008024:Ligands; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D011970:Receptors, Histamine H2; D018100:Receptors, Histamine H3; D012313:RNA; D011899:Ranitidine; D014442:Monophenol Monooxygenase