The role of butyrate in the reverse transformation reaction in mammalian cells

Abstract

The reverse transformation reaction of Chinese hamster ovary cells from compact, epithelial‐like, randomly growing, heavily knobbed, lectin reactive cells into stretched, tighly adherent, smooth‐surfaced, lectin resistant, fibroblast‐like cells normally elicited by dibutyryl cAMP can be produced to its complete extent by N⁶‐monobutyryl cAMP or 8‐bromo‐cAMP. O²‐monobutyryl cAMP is ineffective as is cAMP itself in the absence of an inhibitor of phosphodiesterase activity. In the presence of a phosphodiesterase inhibitor, cAMP is fully effective. These results indicate that the role of the butyryl groups of dibutyryl cAMP and, especially, the N⁶‐butyryl, in the reverse transformation raction is protection of the cAMP analogue from degradation. Butyrate at concentrations of about 1 mM does produce a response which to some extent mimics that of cAMP analogues. The cells, however, fail to assume a fibroblastic‐like shape, but rather become flattened. The butyrate effect is much slower and less readily reversible than that evoked by cAMP analogues. Butyrate produces an approximately 2‐fold increase in intracellular cAMP levels. These results are consistent with the hypothesis that butyrate effects, in part, are mediated by cAMP.