Cis-urocanic acid attenuates histamine receptor-mediated activation of adenylate cyclase and increase in intracellular Ca2+.
UVB irradiation causes suppression of delayed hypersensitivity. Various photoreceptors and mediators of these changes have been proposed, one of which is cis-urocanic acid formed from the naturally occurring trans-urocanic acid in the epidermis on exposure to UV irradiation. The mechanism by which cis-urocanic acid alters the immune system is not fully clarified, but it acts through different mechanisms, perhaps via histamine or histamine-like receptors. Histamine stimulation of keratinocytes induces activation of adenylate cyclase leading to an accumulation of cyclic AMP and an increase in intracellular Ca2+. Thus we investigated the effects of cis-urocanic acid on these transmembrane signaling systems in keratinocytes. Normal human keratinocytes were cultured in serum-free KGM medium. Cyclic AMP was measured by radioimmunoassay. Alterations in intracellular Ca2+ in single living keratinocytes were measured using an inverted fluorescence microscope and an ARGUS-200/CA digital imaging system. Cis-urocanic acid itself did not induce adenylate cyclase activation in cultured normal human keratinocytes. Cis-urocanic acid inhibited histamine-induced cyclic AMP accumulation. It did not affect keratinocyte growth, and did not induce an increase in intracellular Ca2+, but did attenuate the histamine-induced increase in intracellular Ca2+ but not that induced by epinephrine. Cis-urocanic acid acts on keratinocytes via modulation of the effects of histamine.
Department of Dermatology, Hokkaido University School of Medicine, Sapporo, Japan. hkoizumi@med.hokudai.ac.jp
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Koizumi
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Shimizu
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Nishino
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Ohkawara
D000262:Adenylyl Cyclases / Q000187:drug effects* / Q000378:metabolism*; D000322:Adrenergic Agonists / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007424:Intracellular Fluid / Q000737:chemistry; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D011968:Receptors, Histamine / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D014560:Urocanic Acid / Q000494:pharmacology*
D000322:Adrenergic Agonists; D011968:Receptors, Histamine; D014409:Tumor Necrosis Factor-alpha; D006632:Histamine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D014560:Urocanic Acid; D002118:Calcium; D004837:Epinephrine