Substance P induces inositol 1,4,5-trisphosphate and intracellular free calcium increase in cultured normal human epidermal keratinocytes.
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 Ca(2+)-sensitive dye, Fura 2-AM. Treatment of normal human epidermal keratinocytes 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.
Koizumi
H
H
Department of Dermatology, Hokkaido University School of Medicine, Sapporo, Japan.
Yasui
C
C
Fukaya
T
T
Ueda
T
T
Ohkawara
A
A
D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D006801:Humans; D007231:Infant, Newborn; D015544:Inositol 1,4,5-Trisphosphate / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D013373:Substance P / Q000494:pharmacology*
D013373:Substance P; D015544:Inositol 1,4,5-Trisphosphate; D004247:DNA; D002118:Calcium