Abstract

ATP and other adenine derivatives, such as AMP and adenosine, at concentrations above 10(-6) M induced dose-dependent contractions of guinea-pig uterine strips. Treatment of the strips with nonsteroidal anti-inflammatory drugs, such as indomethacin, aspirin and phenylbutazone, at concentrations of 10(-6) to 10(-4) M irreversibly inhibited the contractions, without affecting those caused by acetylcholine and bradykinin. Arachidonic acid (10(-8)-10(-6) g/ml) and prostaglandins (E1, E2 and F2 alpha, 10(-9)-10(-7) g/ml) restored the inhibited uterine response to ATP, but the inhibition was reinstated on washing out of the arachidonic acid or prostaglandins. Furthermore, the prostaglandin antagonists polyphloretin phosphate (3 x 10(-5)-3 x 10(-4) g/ml) and SC 19220 (10(-6)-3 X 10(-5) M) selectively suppressed the action of ATP. In addition to the prostaglandin antagonists, 2,2'-pyridylisatogen, reported to be an ATP antagonist, at concentrations of 10(-6) to 3 x 10(-5) M selectively inhibited the response of uterine strips to ATP. These results suggest the involvement of prostaglandins in the actions of ATP and other adenine derivatives on guinea-pig uterine tissue and provide further evidence for ATP-stimulated prostaglandin formation in smooth muscle.