Effect of cAMP and related compounds on newt epidermal cell migration both in vivo and in vitro.

The effect of cyclic AMP and related compounds on both in vivo and in vitro epidermal cell migration during wound closure in the adult newt was examined. Cyclic AMP (cAMP) and N6,O2'-dibutyryl cyclic AMP (db-cAMP) inhibited migration both in vivo and in vitro when used with equimolar concentrations of theophylline, an inhibitor of 3',5'-cyclic nucleotide phosphodiesterase. Neither db-cAMP nor theophylline alone inhibited migration in vivo. Adenosine 5' monophosphate (AMP), cyclic guanosine 3',5' monophosphate (cGMP) and imidazole, a potentiator of phosphodiesterase were tested in vivo and had no effect on migration. Isoproterenol and epinephrine, which are known to stimulate adenylate cyclase, inhibited migration in vitro. Experiments using the protein synthesis inhibitor, cycloheximide, suggest that cAMP could be acting partially through regulation of protein synthesis but that other factors are involved. Dibutyryl cyclic AMP and theophylline had no effect on the incorporation of 3H-leucine into protein. The inhibition of migration both in vivo and in vitro provides further evidence for a role of cAMP in the regulation of cell motility.