RESEARCH FOR TRANSMEMBRANE SIGNALING SYSTEM OF EPIDERMAL KERATINOCYTES ; INTRACELLULAR FREE CALCIUM AND PROTEIN KINASE C.

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、细胞内游离钙改变、腺苷酸环化酶反应激活。我们阐明缓激肽、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。这些作用是由肌醇1，4，5-三磷酸合成或腺苷酸环化酶激活介导的。钙作为第二信使的重要性。用免疫组化法检测了spectrin、b-fodrin、4.1蛋白样蛋白等膜骨架蛋白在培养角质形成细胞及病变皮肤中的分布变化。本文报道了一种新的用二氢罗丹明123检测角质形成细胞产生过氧化物的方法。nPKC eta和SPRR在正常皮肤和病变皮肤中的表达与分化有关。表达和皮质被膜的形成被认为是介导的激活nPKC eta。角质形成细胞中跨膜信号系统之间的串扰，以及影响这些系统的药物应进行研究。角化异常和增生加速被认为与银屑病的发病密切相关。银屑病患者细胞膜信号系统的改变及治疗药物的作用机制正在研究中。

Epidermal keratinocytes proiferate and differentiate to make stratum corneum. Many chemical mediators, hormones and peptides stimulate keratinocytes to induce phosphophatidylinositol metablism, 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 and diseased skin were observed. A new technique was reported to detect peroxide produced from keratinocytes using dihydrorhodamine 123. Differentiation associated expression of nPKC eta and SPRR was demonstrated in normal and diseased skin. The expression and cornified envelope formation are considered to mediated by activation of nPKC eta.Cross-talk among transmembrane signaling systems in keratinocytes, and drugs to influence these systems should be investigated. Abnormal keratinization and accerelation 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.