Pharmacological classification of receptors for adenyl purines in guinea pig myometrium.
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.
Smith
M A
MA
Department of Pharmacology, University of Nevada School of Medicine, Reno.
Buxton
I L
IL
Westfall
D P
DP
D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001386:Azides / Q000494:pharmacology; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D009215:Myometrium / Q000032:analysis / Q000187:drug effects*; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000032:analysis / Q000187:drug effects*; D013237:Stereoisomerism; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013872:Thionucleosides / Q000494:pharmacology
C012761:3'-O-(3-(N-(4-azido-2-nitrophenyl)amino)propionyl)adenosine-5'-triphosphate; D001386:Azides; D011983:Receptors, Purinergic; D013872:Thionucleosides; D006151:Guanosine; C002121:6-(4-nitrobenzylthio)guanosine; D015762:2-Chloroadenosine; D010660:Phenylisopropyladenosine; D000255:Adenosine Triphosphate; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate