Regulation of Stimulated Cyclic AMP Synthesis by Urocanic Acid

Urocanic acid (UCA) has been shown to mediate the UVB radiation-induced immunosuppression initiated i'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 stud was undertaken to determine the effect of trans - and cis UCA on cyclic adenosine 3',5'-monophosphate (cAMP synthesis in human dermal fibroblasts, Golden Syria'hamster hepatocytes and in the human adenocarcinoms cell line, HT29. Neither trans - nor cis -UCA was able is stimulate cAMP synthesis directly in any of the model: tested. In human dermal fibroblasts, cis -UCA, in contras to trans -UCA, specifically inhibited cAMP synthesis in duced by either prostaglandin (PG) El or PGE2 with s maximum inhibitory effect of 25-30% at cis -UCA con centrations greater than 1 μ M and half-maximum inhib itory effect (ECso) observed at 35 n M . The effect of cis -UCA was not to stimulate phosphodiesterase and cAMP breakdown. The inhibitory effect of cis -UCA (an imid azole derivative) was not mediated through stimulatiot of the α2-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 fibroblast were confluent or postconfluent. In contrast to the studie with human dermal fibroblasts, an inhibitory effect of cis -UCA was not observed in either isolated hamster he patocytes or HT29 cells, in which cAMP synthesis wa 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.