Substance P induces inositol 1,4,5-trisphosphate and intracellular free calcium increase in cultured normal human epidermal keratinocytes |
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Authors: | Hiroko Koizumi Chikako Yasui Torn Fukaya Tetsuo Ueda Akira Ohkawara |
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Institution: | Department of Dermatology. Hokkaido University School of Medicine, Sapporo, Japan;Faculty of Pharmacology, Hokkaido University, Sapporo, Japan |
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Abstract: | Abstract Substance P is a neuropeptide which is present in peripheral C nerve endings and released from them. Free nerve endings of C nerve are present in human epidermis. The effects of substance P on the transmembrane signaling system of pig epidermal sheets were previously reported. In these studies, a small amount of cells other than keratinocytes contaminated the epidermal sheets and the species difference from human was also noticed. Therefore we investigated the effects of substance P on cultured normal human epidermal keratinocytes. Alteration of intracellular free calcium (Ca2+) in single living keratinocytes was studied using an inverted fluorescence microscope and Ca2+ -sensitive dye, Fura 2-AM. Treatment of normal human epidermal kertinocytes with substance P resulted in an increase in inositol 1,4,5-trisphosphate and in intracellular Ca2+. Substance P inhibited DNA synthesis of the keratinocytes in a dose-dependent manner. These results are consistent with the view that substance P stimulates phosphatidylinositol-4,5-bisphosphate hydrolysis of human keratinocytes, resulting in inositol 1,4,5-trisphosphate-Ca2+ signal. |
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Keywords: | substance P keratinocyte inositol 1 4 5-trisphosphate calcium neuropeptide human |
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