Abstract

The sensitivity of the smooth muscle of in vitro strips of guinea pig uterus to the contractile-inducing effects of a series of adenyl purines was investigated. Both P1-purinoceptor agonists, such as 2-chloroadenosine, and P2-purinoceptor agonists, such as beta,gamma-methylene ATP, produced concentration-dependent contractions. Responses to 2-chloroadenosine were antagonized by the P1-receptor antagonist 8-phenyltheophylline and those to beta,gamma-methylene ATP by the P2-receptor antagonist 3'-O-3-[N-(4-azido-2-nitrophenyl)amino]propionyl ATP. Significant antagonism of responses to ATP occurred only with combined treatment with 8-phenyltheophylline and 3'-O-3-[4-azido-2-nitrophenyl)amino]propionyl ATP. Responses to both adenosine and ATP were potentiated significantly in the presence of the adenosine uptake blocker S-p-nitrobenzyl-6-thioguanosine. These results indicate the presence of both P1- and P2-receptors in the myometrium and that activation of either receptor leads to contraction. Additional studies with other adenosine analogs, such as 5'-N-ethyl-carboxamine adenosine, R-N6-phenylisopropyladenosine, S-N6-phenylisopropyladenosine and N6-cyclohexyladenosine, indicate that the P1-receptor is of the A1 subtype.