Transmembrane signaling system concerning super oxide production

UVB照射可抑制迟发型超敏反应。这些变化的光感受器和介体已经被提出，其中之一是在紫外线照射下，表皮中自然产生的反式尿毒酸形成的顺式尿毒酸。顺式尿囊酸改变免疫系统的机制尚不完全清楚。尿毒酸通过不同的机制起作用，可能是通过组胺或类似组胺的受体。角质形成细胞受到组胺刺激，激活腺苷环化酶，积聚环磷酸腺苷，细胞内钙离子增加。因此，我们研究了顺式尿囊酸对角质形成细胞中这些跨膜信号系统的影响。正常人角质形成细胞在无血清KGM培养液中培养。用放射免疫法测定环磷酸腺苷。用倒置荧光显微镜和Argus-200/CA数字成像系统检测单个活体角质形成细胞内钙离子的变化。顺尿酸本身不能诱导培养的正常人角质形成细胞的腺苷酸环化酶激活。顺式尿苷酸抑制组胺诱导的环磷酸腺苷蓄积。顺铂不影响角质形成细胞的生长。顺式尿囊酸不能引起细胞内钙离子的升高。顺尿酸可减弱组胺引起的细胞内钙升高，但不能减弱肾上腺素引起的细胞内钙升高。顺尿酸对角质形成细胞的作用是通过对组胺作用的调节来揭示的。

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 trans-urocanic acid in the epidermis naturally occurring on exposure to UV irradiation. The mechanism by which cis-urocanic acid alters the immune system is not fully clarified. Urocanic acid acts through different mechanisms, perhaps via histamine or histamine-like receptors. Histamine stimulation of keratinocytes induces activation of adenylate cyclase to accumulate cyclic AMP and an increase of 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. The alterations of 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 cyclic AMP accumulation by histamine. Keratinocyte growth was not affected by cis-urocanic acid. Cis-urocanic acid did not induce an increase of intracellular Ca2+. Cis-urocanic acid attenuated the histamine induced increase in intracellular Ca2+ but not that induced by epinephrine. The effects of cis-urocanic acid on keratinocytes are revealed through modulation of effects of histamine.