Cyclic AMP as a mitotic signal for epidermal keratinocytes, but not for dermal fibroblasts.

Abstract

The function of cyclic AMP in the growth of epidermal and dermal cells was investigated. Cholera toxin was used to increase the amount of intracellular cyclic AMP. This toxin had a stimulatory effect on human epidermal cells only when growth was limited; i.e., when a small number of cells was plated for colony formation, when cells from frozen stock were cultured, and when cells were in the initial phase of primary culture. Cholera toxin, however, had no significant effect on the growth rate during exponential growth or on the saturation density during the stationary phase.The stimulatory effect of the toxin was specific to epidermal keratinocytes. In other types of cells, the effect varied : with human dermal fibroblasts there was no ffeect, or some inhibition.A membrane receptor for cholera toxin, GM 1 ganglioside, was isolated from human epidermal cells. Cyclic AMP was induced markedly by cholera toxin in human epidermal keratinocytes, which suggests that an increase in the amount of cyclic AMP may act as a mitotic signal in these cells. Cholera toxin also induced cyclic AMP in human dermal fibroblasts irrespective of the growth response, an indication that in dermal fibroblasts the content of cyclic AMP is not necessarily related to the proliferation of the cells.