Phorbol esters enhance the cyclic GMP response of T84 cells to the heat-stable enterotoxin of Escherichia coli (STa)
Autor: | C P Chambers, E. L. Hewlett, John K. Crane, C S Weikel, J Linden, C L Spann |
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Rok vydání: | 1990 |
Předmět: |
Time Factors
Bacterial Toxins Immunology In Vitro Techniques Biology digestive system Microbiology Cell Line Enterotoxins Intestinal mucosa Phorbol Esters Escherichia coli Humans Heat-stable enterotoxin Intestinal Mucosa Phosphodiesterase inhibitor Cyclic GMP Protein Kinase C Protein kinase C chemistry.chemical_classification Dose-Response Relationship Drug Escherichia coli Proteins Drug Synergism Epithelial Cells Molecular biology Infectious Diseases Enzyme chemistry Biochemistry Guanylate Cyclase Cell culture Second messenger system Parasitology Signal transduction Research Article |
Zdroj: | Infection and Immunity. 58:1402-1407 |
ISSN: | 1098-5522 0019-9567 |
DOI: | 10.1128/iai.58.5.1402-1407.1990 |
Popis: | We examined the effect of protein kinase C (PKC) activation on the cyclic GMP response to heat-stable enterotoxin (STa) in a colonic carcinoma intestinal epithelial cell line, T84 cells. Our results demonstrate that the active phorbol ester analog, phorbol dibutyrate, but not the inactive alpha-phorbol dibutyrate, acts synergistically with STa to elevate cyclic GMP in intact T84 cells. The effect is observed in the absence or presence of the phosphodiesterase inhibitor, isobutylmethylxanthine, which suggests that phorbol dibutyrate modifies cyclic GMP synthesis rather than cyclic GMP degradation. In contrast to several systems in which prolonged treatment with phorbol ester desensitizes PKC-mediated responses, the cyclic GMP response in T84 cells is not diminished by prolonged treatment of T84 cells with phorbol dibutyrate. Also, transient treatment of T84 cells with phorbol dibutyrate enhances subsequent STa-stimulated cyclic GMP accumulation. These observations suggest that PKC activation produces a long-lived signal in T84 cells which enhances cyclic GMP accumulation in response to STa. Second messenger "cross talk" [T. Yoshimasa, D. R. Sibley, M. Bouvier, R. J. Lefkowitz, and M. G. Caron, Nature (London) 327:67-70, 1987] may be important in the pathogenesis of diarrheal disease. |
Databáze: | OpenAIRE |
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