Fluvastatin Enhances Receptor-Stimulated Intracellular Ca2+Release in Human Keratinocytes

• Published in: Biochemical and biophysical research communications Vol. 245; no. 2; pp. 307 - 312
• Main Authors: Coutant, Karine D., Wolff-Winiski, Barbara, Ryder, Neil S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17-04-1998
• Subjects: Aniline Compounds - metabolism; Bradykinin - pharmacology; Calcium - metabolism; Cell Line; Dinoprostone - biosynthesis; Epidermal Growth Factor - pharmacology; Fatty Acids, Monounsaturated - pharmacology; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Indoles - pharmacology; Keratinocytes - drug effects; Kinetics; Mevalonic Acid - metabolism; Thapsigargin - pharmacology; Xanthenes - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1998.8429

We analyzed the effect of isoprenoid depletion by fluvastatin on bradykinin (BK)- and epidermal growth factor (EGF)-mediated Ca2+mobilization and prostaglandin E2 production, in the human keratinocyte cell line HaCaT. BK and EGF stimulated Ca2+mobilization in an agonist-dependent manner. The synthesis of prostaglandin E2 paralleled the level of Ca2+mobilization induced by BK and EGF. Treatment with fluvastatin increased the EGF-promoted but not the BK-promoted Ca2+mobilization and prostaglandin E2 production in Ca2+-containing medium. In the absence of extracellular Ca2+, fluvastatin treatment led to an increase in intracellular Ca2+release by both agonists. This effect was abolished by depleting the intracellular pool of Ca2+with thapsigargin. Our findings showed that the intracellular Ca2+release was dependent on the metabolism of mevalonate and that the Ca2+mobilization modulated prostaglandin E2 synthesis in human keratinocytes.