Regulation of cyclic nucleotide phosphodiesterase activity in myometrium from pregnant and spayed rhesus monkeys

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Abstract
The activities of myometrial cyclic nucleotide phosphodiesterases (PDE) and the sensitivity of these enzymes to the effector molecules c[cyclic]GMP and c[cyclic]AMP, were determined in the 100,000 g supernatant of homogenates from pregnant and spayed rhesus monkeys. The specific activities (per mg N) of the myometrial cyclic nucleotide PDE in the supernatant from spayed monkeys were higher than those from pregnant monkeys at all substrate levels studied. 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 .mu.M cAMP low levels of cGMP (0.1-1.0 .mu.M) caused the same percentage increase in cGMP-PDE activity in both tissues. At high substrate levels of 100 .mu.M cAMP, 1 .mu.M cGMP inhibited only the cAMP-PDE from spayed monkeys, and the enzyme from spayed monkeys was more effectively inhibited by 10 and 40 .mu.M cGMP than was the enzyme from pregnant animals. The cGMP-PDE activity was inhibited by cAMP (1.0-50.0 .mu.M), and the percentage inhibition with increasing levels of cAMP appeared to be similar in the 2 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. cAMP and cGMP may each be involved in regulating the degradation of the other nucleotide in rhesus myometrium.