Regulation of cyclic nucleotide phosphodiesterase activity in rhesus fetal muscle

In both fetal and adult rhesus muscle, low levels of guanosine 3':5'-monophosphate (cyclic GMP; 0.25--5.0 micrometer) stimulated the adenosine 3':5'-monophosphate (cyclic AMP)-phosphodiesterase (PDE) at low substrate levels; the fetal enzyme was more sensitive than the adult (supernatant and particulate fractions). At high levels of substrate cyclic AMP (25--100 micrometer), hydrolysis was not influenced by either 10 or 20 micrometer cyclic GMP but the fetal and adult series were equally inhibited by 40 micrometer cyclic GMP. In the supernatant fraction cyclic AMP inhibition of cyclic GMP hydrolysis increased with increasing cyclic AMP levels. There was no difference between fetal and adult muscle preparations in percent inhibition; however, in the adult series, the inhibition was noncompetitive whereas in the fetal series the inhibition was competitive. The Ki for cyclic AMP was 40 micrometer for fetal and 100 micrometer for adult cyclic GMP-PDE. The Vmax values for cyclic GMP-PDE and both cyclic AMP-PDE enzymes were higher in the fetal series.