The effects of some possible inhibitors of ectonucleotidases on the breakdown and pharmacological effects of ATP in the guinea-pig urinary bladder.
1. The effects of some possible inhibitors of ectonucleotidases on the breakdown of extracellular ATP by strips of guinea-pig urinary bladder were investigated. 2. Suramin and ethacrynic acid (10 mM) both inhibited ATP breakdown significantly, and difluorodinitrobenzene (10 mM) inhibited it slightly whereas N-ethylmaleimide, adenosine 5'-(gamma-thiotriphosphate) (ATP-gamma-S) and reactive blue-2 (10 mM) were without effect. 3. The inhibitory effects of suramin on ATP breakdown were non-competitive. 4. Ethacrynic acid (1 mM) irreversibly inhibited contractions of the guinea-pig bladder induced by ATP, substance P, histamine, non-adrenergic, non-cholinergic nerve stimulation or KCl, whereas suramin (100 microM) had no inhibitory effect. 5. The results suggest that suramin might provide a starting point for the design of selective inhibitors of ectonucleotidases.
Hourani
S M
SM
Department of Biochemistry, University of Surrey, Guildford, England.
Chown
J A
JA
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D004139:Dinitrofluorobenzene / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D004976:Ethacrynic Acid / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006207:Half-Life; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D009708:Nucleotidases / Q000037:antagonists & inhibitors*; D011189:Potassium Chloride / Q000494:pharmacology; D013498:Suramin / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism
C022571:adenosine 5'-O-(3-thiotriphosphate); D013498:Suramin; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D004139:Dinitrofluorobenzene; D009708:Nucleotidases; C002041:1,5-difluoro-2,4-dinitrobenzene; D004976:Ethacrynic Acid; D005033:Ethylmaleimide