| Autor: |
B, Bouscarel, F, Noonan, S, Ceryak, T W, Gettys, T M, Phillips, E C, DeFabo |
| Rok vydání: |
1998 |
| Předmět: |
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| Zdroj: |
Photochemistry and photobiology. 67(3) |
| ISSN: |
0031-8655 |
| Popis: |
Urocanic acid (UCA) has been shown to mediate the UVB radiation-induced immunosuppression initiated in the skin by UV-induced isomerization from the trans to the cis isomer. However, the mechanism by which cis-UCA acts is still unclear. Therefore, the present study was undertaken to determine the effect of trans- and cis-UCA on cyclic adenosine 3',5'-monophosphate (cAMP) synthesis in human dermal fibroblasts, Golden Syrian hamster hepatocytes and in the human adenocarcinoma cell line, HT29. Neither trans- nor cis-UCA was able to stimulate cAMP synthesis directly in any of the models tested. In human dermal fibroblasts, cis-UCA, in contrast to trans-UCA, specifically inhibited cAMP synthesis induced by either prostaglandin (PG) E1 or PGE2 with a maximum inhibitory effect of 25-30% at cis-UCA concentrations greater than 1 microM and half-maximum inhibitory effect (EC50) observed at 35 nM. The effect of cis-UCA was not to stimulate phosphodiesterase and cAMP breakdown. The inhibitory effect of cis-UCA (an imidazole derivative) was not mediated through stimulation of the alpha 2-adrenergic receptor. The inhibitory effect of cis-UCA on stimulated cAMP synthesis was a function of the cell density and was only significant when the fibroblasts were confluent or postconfluent. In contrast to the studies with human dermal fibroblasts, an inhibitory effect of cis-UCA was not observed in either isolated hamster hepatocytes or HT29 cells, in which cAMP synthesis was stimulated by glucagon and vasoactive intestinal peptide, respectively. These results point to a possible regulation of cAMP synthesis in fibroblasts as one mechanism by which cis-UCA exerts its biological effect in the skin. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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