The effects of P2Y receptor agonists and adenosine on prostaglandin production by the guinea-pig uterus.

1. This study has investigated the effects adenosine 5'-triphosphate (ATP), analogues of ATP, uridine 5'-triphosphate (UTP) and adenosine on prostaglandin output from the guinea-pig uterus superfused in vitro, and from guinea-pig endometrium and myometrium cultured for 24 h. 2. ATP, 2-methylthio ATP and adenosine increased the outputs of prostaglandin F(2 alpha) (PGF(2 alpha)) and 6-keto-PGF(1 alpha) (reflecting PGI(2) production), and UTP increased the output of PGF(2 alpha) from the superfused guinea-pig uterus. These findings support the hypothesis that the contractile effects of ATP, 2-methylthio ATP, UTP and adenosine are mediated by prostaglandins. 3. Suramin (a P2 receptor antagonist) and 8-sulphophenyltheophylline (an A receptor antagonist) blocked the stimulatory actions of ATP and adenosine, respectively, on PGF(2 alpha) output, suggesting that ATP acts on P2 receptors (probably of the P2Y type) and adenosine acts on A receptors in the guinea-pig uterus to increase PGF(2 alpha) production. 4. ATP, 2-methylthio ATP, alpha,beta-methylene ATP, beta,gamma-methylene ATP, UTP and adenosine increased the output of PGF(2 alpha) from guinea-pig endometrium and myometrium after 24 h of culture, with a greater stimulatory effect being exerted on the endometrium than on the myometrium. Little or no stimulatory effect was seen after 2 and 8 h of culture. In addition the effects of ATP, ATP analogues, UTP and adenosine on the outputs of PGE(2) and 6-keto-PGF(1 alpha) from cultured endometrium and myometrium were more variable, with both stimulation and inhibition being observed. 5. The stimulatory effects of ATP and adenosine on PGF(2 alpha) output from the endometrium and myometrium were associated with an increase in the prostaglandin synthesizing capacity of both tissues, due probably to an increase in the amount of prostaglandin H synthase present.