RESEARCH FOR TRANSMEMBRANE SIGNALING SYSTEM OF EPIDERMAL KERATINOCYTES; INTRACELLULAR FREE CALCIUM AND CELLULAR RESPONSES.

表皮角质形成细胞增殖分化，形成角质层。许多化学介质、激素和多肽刺激角质形成细胞诱导磷脂酰肌醇代谢，改变细胞内游离钙，激活腺苷环化酶反应。我们阐明了缓激肽、凝血酶、P物质、β-肾上腺素、腺苷和组胺诱导细胞内游离钙增加。这些作用是通过合成肌醇1，4，5-三磷酸或腺苷环化酶激活来实现的。显示了钙作为第二信使的重要性。免疫组织化学检测膜骨架蛋白SPECTIN、b-fodrin、4.1蛋白样蛋白的存在，并观察其在角质形成细胞中的分布随培养液中钙离子浓度的变化。报道了一种用二氢罗丹明123检测角质形成细胞产生的过氧化氢的新技术。角质形成细胞跨膜信号系统之间的串扰，以及影响这些信号系统的药物有待研究。角化异常和增殖加速被认为与银屑病的发病密切相关。银屑病中膜信号系统的改变以及治疗皮肤病的药物的作用机制正在研究中。

Epidermal keratinocytes proliferate and differentiate to make stratum corneum. Many chemical mediators, hormones and peptides stimulate keratinocytes to induce phosphophatidylinositol metabolism, alteration of intracellular free calcium, adenylate cyclase response activation. We elucidated that bradykinin, thrombin, substance P, beta-adrenarin, adenosine, and histamine induce increase of intracellular free calcium. These effects are mediated with synthesis of inositol 1,4,5-trisphosphate or adenylate cyclase activation. The importance of calcium as a second messenger is shown. Presence of membrane skeleton proteins such as spectrin, b-fodrin, 4.1 protein like proteins were detected immunologically and the alteration of their distribution in cultured keratinocytes were observed with the change of calcium concentration of the medium. A new technique was reported to detect peroxide produced from keratinocytes using dihydrorhodamine 123.Cross-talk among transmembrane signaling systems in keratinocytes, and drugs to influence these systems should be investigated. Abnormal keratinization and acceleration of proliferation are considered to closely realt to pathogenesis of psoriasis. The alteration of membrane signaling systems in psoriasis and the action mechanisms of the drugs used in therapy of skin diseases are under investigation.