Stimulation of Adenosine 3',5'-Monophosphate Hydrolysis by Guanosine 3',5'-Monophosphate

Abstract

Abstract Guanosine 3',5'-monophosphate (cyclic GMP) increased the rate of adenosine 3',5'-monophosphate (cyclic AMP) hydrolysis by phosphodiesterase preparations from several tissues. Stimulation of cyclic AMP hydrolysis occurred with initial concentrations of cyclic GMP as low as 0.08 µm and was seen with particulate phosphodiesterase preparations from rat liver, brain, kidney, heart, and thymus and with soluble preparations from liver and thymus. Higher concentrations of cyclic GMP (g 50 µm) were inhibitory to cyclic AMP hydrolysis in rat liver extracts. Inosine 3',5'-monophosphate (cyclic IMP) also stimulated the hydrolysis of cyclic AMP but was somewhat less effective than cyclic GMP. 5'-GMP,5'-IMP, uridine 3',5'-monophosphate, thymidine 3',5'-monophosphate, and guanosine had no effect. Cyclic AMP and cyclic IMP inhibited the hydrolysis of cyclic GMP by liver supernatant fractions. Fractionation of rat liver extracts with ammonium sulfate yielded one fraction of phosphodiesterase activity that was stimulated by cyclic GMP and one that was not. The stimulatory effect of cyclic GMP on cyclic AMP hydrolysis by soluble and particulate liver phosphodiesterases was not seen in the presence of the nonionic detergents Triton X-100 or Lubrol PX.