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MA Smith, IL Buxton and DP Westfall
Department of Pharmacology, University of Nevada School of Medicine, Reno.
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.