Contraction and prostaglandin biosynthesis by myometrium from non-pregnant and pregnant rabbits in response to adenosine 5'-triphosphate.

In both non-pregnant and pregnant rabbit myometrial strips, adenosine 5'-triphosphate (ATP) produced contractions in a concentration-dependent manner. Furthermore, ATP (100 microM and 1 mM) produced an initial rapid twitch-like contraction followed by augmented spontaneous motility. These contractile responses of strips from pregnant rabbits to ATP were more marked than those of strips from non-pregnant rabbits. The pD2 values for the contractile response to ATP were 5.20 and 6.70 in strips from non-pregnant and pregnant rabbits, respectively. Treatment with indomethacin did not affect the initial rapid twitch-like contraction, but inhibited the augmented spontaneous motility. ATP also increased the synthesis of prostaglandins (PGs) and thromboxane B2 (TXB2) in a concentration-dependent manner in the following order: 6-keto-PGF1 alpha greater than PGE2 greater than PGF2 alpha greater than TXB2. The increase in the synthesis of cyclooxygenase products induced by ATP was more marked in strips from pregnant rabbits than in strips from non-pregnant rabbits. ATP and melittin stimulated arachidonic acid, phosphatidic acid and diacylglycerol formation in strips from both non-pregnant and pregnant rabbits. These results indicate that ATP stimulates PGs and TXB2 synthesis and phosphatidylinositol hydrolysis through an effect on P2-purinoceptors and consequently augments myometrial contractility in both non-pregnant and pregnant rabbits.