The activities of myometrial cyclic nucleotide phosphodiesterases (PDEs) and the sensitivity of these enzymes to the effector molecules, cGMP and cAMP, were determined in the 100,000 g supernatant of homogenates from pregnant and spayed rhesus monkeys. The specific activities (per mg nitrogen) of the myometrial cyclic nucleotide PDEs in the supernatant from spayed monkeys were higher than those from pregnant monkeys at all substrate levels studied. However, when calculated on the basis of the DNA content of the myometrium, which was 8 times higher in the spayed than in the pregnant animals, the specific activities were lower in the tissue from spayed animals. At substrate levels of 2 . 5 micron-cAMP, low levels of cGMP (0 . 1-1 . 0 micron) caused the same percentage increase in cGMP-PDE activity in both tissues. At high substrate levels of 100 micron-cAMP, 1 micron-cGMP inhibited only the cAMP-PDE from spayed monkeys, and the enzyme from spayed monkeys was more effectively inhibited by 10 and 40 micron-cGMP than was the enzyme from pregnant animals. The cGMP-PDE activity was inhibited by cAMP (1 . 0-50 . 0 micron), and the percentage inhibition with increasing levels of cAMP appeared to be similar in the two series. The levels of cGMP and cAMP that modify the rate of hydrolysis of the other nucleotide in rhesus myometrium seem to be within the physiological range for these compounds in situ. It therefore appears possible that cAMP and cGMP are each involved in regulating the degradation of the other nucleotide in rhesus myometrium.
In both fetal and adult rhesus muscle, low levels of guanosine 3’:5’-monophosphate (cyclic GMP; 0.25–5.0 μM) 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 μM), hydrolysis was not influenced by either 10 or 20 μM cyclic GMP but the fetal and adult series were equally inhibited by 40 μM 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 μM for fetal and 100 μM for adult cyclic GMP-PDE. The Vmax values for cyclic GMP-PDE and both cyclic AMP-PDE enzymes were higher in the fetal series.
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