The activity of phosphorothioate analogues of ATP in various smooth muscle systems.
Phosphorothioate analogues of adenosine 5'-triphosphate (ATP) have been tested on the rat and guinea-pig vas deferens, the guinea-pig taenia coli and urinary bladder. Adenosine 5'0-(2-thiotriphosphate) (ATP beta S) was more active than adenosine 5'0(1-thiotriphosphate) (ATP alpha S) and ATP in producing contractile responses on the vas deferens of rat and guinea-pig, and guinea-pig bladder, though the difference of potency was less marked for producing relaxation of the carbachol-contracted taenia coli. No differences were observed between the A and B diastereoisomers of ATP alpha S or ATP beta S. Contractions of the vas deferens produced by ATP alpha S were of much longer duration than those produced by ATP beta S. When tested against electrically-evoked twitch responses of the vas deferens the order of potencies was reversed with ATP being most active and ATP beta S least active. These inhibitory effects were blocked by 8-phenyl-theophylline. The calculated pA2 values for ATP, adenosine, beta, gamma-methylene ATP (APPCP) and ATP alpha S were similar, suggesting a common site of action. The results do not reveal any stereoselectivity among the tissues tested, for the diastereoisomers of ATP phosphorothioates; the observed differences of potency may be due to differences between ATP alpha S and ATP beta S in their rates of metabolism to adenosine. The different response profiles to the phosphorothioates may however reflect some differences of receptor mechanisms.
D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007420:Intestine, Large / Q000187:drug effects; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D051381:Rats; D013873:Thionucleotides / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects
D013873:Thionucleotides; C017817:adenosine 5'-(1-thio)triphosphate; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D000241:Adenosine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate