Phorbol esters affect cyclic nucleotide-mediated responses in cultured chick lens annular pad cells

Cultured chick lens annular pad cells were treated with a lipid soluble cAMP analog, the phorbol ester TPA or a combination of the two compounds in order to assess their effects on mitotic activity, cell spreading and the accumulation of differentiation marker proteins. Both 8b-cAMP and TPA were individually able to inhibit mitotic activity in cells cultured in the presence of 5% serum. The combination of the two produced a greater degree of mitotic inhibition. Both compounds were also able to inhibit cellular spreading onto laminin coated surfaces. Opposite effects on the accumulation of differentiation marker proteins were observed for the two compounds. While 8b-cAMP increased levels of marker proteins, TPA or the combination of TPA and 8b-cAMP reduced levels of marker proteins. These data indicate that crosstalk between two distinct signal transduction systems in the lens is able to influence cell behaviors implicated in the development of secondary or posterior subcapsular cataract. In addition, these data demonstrate that both positive and negative regulatory influences affect the accumulation of differentiated characteristics.