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

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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.