Stimulation of phosphatidylinositol hydrolysis, diacylglycerol release, and gene expression in response to endothelin, a potent new agonist for fibroblasts and smooth muscle cells.

摘要: Abstract Endothelin is a potent vasoconstrictive peptide recently isolated by Yanagisawa, M., Kurihara, H., Kimura, S., Tamobe, Y., Kobayashi, Mitsui, Yazaki, Goto, K., and Masaki, T. (1988) Nature 332, 411-415). In order to understand the mechanism of action endothelin in various cell types we have examined effects on second messenger levels Rat-1 fibroblasts A10 smooth muscle cells. stimulated 15-fold increase accumulation inositol trisphosphate cells, with half-maximal stimulation observed at 0.5 nM endothelin. vascular line, phosphatidylinositol turnover more than 3-fold, comparable produced serum. Concurrent phosphate release, increased diacylglycerol 50% cells 3-fold The response was equal or greater Stimulation did not require presence extracellular calcium blocked treatment EGTA cobalt. Furthermore, stimulate Ca2+ uptake either type actually reduced below control duration preincubation. an intracellular levels, from 100 over 750 150 350-nM as measured fura-2 microspectrofluorimetry. rise concentration inhibited These data indicate that act open channels Cytoplasmic VL30 RNA, gene independently induced protein kinase C epidermal growth factor, were following treatment, even C-depleted We conclude very stimulus for turnover, transcription. may wide-ranging implications number disease states.