Increased cholera toxin-, and forskolin-induced cyclic AMP accumulations in psoriatic involved versus uninvolved or normal human epidermis.
Increased cholera toxin-, and forskolin-induced cyclic AMP accumulations in psoriatic involved versus uninvolved or normal human epidermis.
复制标题
与未受累或正常人表皮相比，受累银屑病患者的霍乱毒素和毛喉素诱导的环 AMP 积累增加。
DOI：
10.1111/1523-1747.ep12464401
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
N. Ohkuma
中科院分区：
文献类型：
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作者：
H. Iizuka;S. Matsuo;T. Tamura;N. Ohkuma
银屑病累及的表皮显示不同的受体-腺苷酸环化酶反应改变;其中最突出的是β-肾上腺素能腺苷酸环化酶反应缺陷，其通常是人表皮的主要受体-腺苷酸环化酶系统。已知腺苷酸环化酶（一种膜结合酶复合物）的激活需要至少3个不同亚基的功能偶联：1）受体亚基（R），2）鸟嘌呤核苷酸结合蛋白（G），和3）催化亚基（C）。然而，银屑病表皮中β-肾上腺素能缺陷的确切性质仍有待确定，特别是在G和C功能方面。采用银屑病患者皮损和非皮损皮肤，研究了霍乱毒素（监测G-C相互作用）和毛喉素（监测C功能）对表皮腺苷酸环化酶系统的影响，并与正常人表皮进行了比较。这两种药物都增加了参与，未参与和正常人表皮的环AMP水平。在存在环核苷酸磷酸二酯酶抑制剂异丁基甲基黄嘌呤（IBMX）的情况下观察到显著蓄积;在不存在磷酸二酯酶抑制剂的情况下，每种药物的影响极小。霍乱毒素作用的比较显示，银屑病累及表皮比未累及表皮积累更多的环AMP（累及：193 +/- 65;未累及：117 +/- 54 pmole/mg蛋白/5 h）。同样，毛喉素诱导的受累表皮的环磷酸腺苷积累也远高于未受累表皮（受累：374 +/- 152;未受累：101 +/- 41 pmoles/mg蛋白/2 h）。正常人表皮的那些与未受累表皮的那些没有显著差异（霍乱毒素：99 +/- 36 pmoles/mg蛋白质/5 h;毛喉素：84 +/- 22 pmoles/mg蛋白质/2 h）。我们的研究结果表明，G和C的功能和它们的相互作用是没有缺陷（而是增加）在银屑病涉及的表皮。这表明银屑病累及表皮的β-肾上腺素能反应缺陷反映了表皮腺苷酸环化酶系统的R或R-G相互作用缺陷。
Psoriatic involved epidermis reveals variously altered receptor-adenylate cyclase responses; among them the most prominent is defective beta-adrenergic adenylate cyclase response, which is normally the major receptor-adenylate cyclase system of human epidermis. It is known that activation of hormone-stimulated adenylate cyclase, a membrane-bound enzyme complex, requires functional coupling of at least 3 distinct subunits: 1) receptor subunit (R), 2) guanine nucleotide binding protein (G), and 3) catalytic subunit (C). The precise nature of the beta-adrenergic defect in the psoriatic epidermis, however, remains to be determined, especially in terms of G and C function. Using the involved and uninvolved skin from psoriatic patients, we investigated effects of cholera toxin (which monitors G-C interaction) and forskolin (which monitors C function) on the adenylate cyclase system of epidermis, which were compared with those of normal human epidermis. Both agents increased cyclic AMP levels of involved, uninvolved, and normal human epidermis. Marked accumulations were observed in the presence of cyclic nucleotide phosphodiesterase inhibitor, isobutyl-methylxanthine (IBMX); without the phosphodiesterase inhibitor, the effect of each agent was minimal. Comparison of the effects of cholera toxin revealed that the psoriatic involved epidermis accumulates much more cyclic AMP than the uninvolved epidermis (involved: 193 +/- 65; uninvolved: 117 +/- 54 pmoles/mg protein/5 h). Similarly forskolin-induced cyclic AMP accumulations of the involved epidermis were much more than those of uninvolved epidermis (involved: 374 +/- 152; uninvolved: 101 +/- 41 pmoles/mg protein/2 h). Those of normal human epidermis were not significantly different from those of uninvolved epidermis (cholera toxin: 99 +/- 36 pmoles/mg protein/5 h; forskolin: 84 +/- 22 pmoles/mg protein/2 h). Our results indicate that G and C function and their interaction is not defective (but rather increased) in the psoriatic involved epidermis. This suggests that the defective beta-adrenergic response of psoriatic involved epidermis reflects defective R or R-G interaction of the epidermal adenylate cyclase system.