Effects of dinitrophenol on phosphorylase a activity, adenine nucleotide levels and tension in rabbit colon smooth muscle.

Glycogen phosphorylase a activity, the contents of adenine nucleotides and isometric tension were measured in rabbit colon smooth muscle after exposure to 2,4-dinitrophenol (DNP). DNP caused a dose-dependent increase in phosphorylase a activity, with an ED50 value of 1 X 10(-4)M. Since adenine nucleotides, especially 5-AMP by inhibiting the phosphorylase a to b conversion, might increase the phosphorylase a activity, a time-response study was undertaken in order to analyse the time course of changes in the adenine nucleotide content and phosphorylase a activity after addition of DNP. The latter activity was increased after only 1 min. of incubation. At this time no changes were found in the contents of ATP, ADP, 5-AMP or CP. Not until the phosphorylase a activity had reached its maximum after 5-7.5 min. did the 5-AMP content increase. The phosphorylase a activity then started to decline, but the 5-AMP content continued to rise. The effect of DNP on isometric tension was also studied to test whether the cytoplasmic Ca2+ concentration was increased. An increase in tension was observed 5 min. after administration of the drug and was maximal at 15 min. The results seem to dispute against 5-AMP as being a mediator for the DNP-stimulated increased in phosphorylase a activity in smooth muscle. The finding that DNP elicited a contraction of rabbit colon supports the earlier suggestion that the cytoplasmic Ca2+ concentration was increased (Pettersson 1983).