Inhibition of rat parotid ecto-ATPase activity.
The inhibitory profile of several known and suspected ecto-ATPase inhibitors was compared on ecto-ATPase activity in rat parotid plasma membranes. Those chemicals with high IC50 (above 130 microM) were the nucleotides alpha,beta-methylene ATP, beta,gamma-methylene ATP, 2-methylthio ATP, inosine triphosphate, 5'-p-fluorosulphonylbenzoyladenosine, the sulphonates, 1-amino-2-naphthol-4-sulphonic acid, Coomassie brilliant blue G, and the stilbene disulphonates, DIDS and SITS. Those agents with low IC50 were: Coomassie brilliant blue R (114 microM), ATPgammaS (49 microM), suramin (72 microM) and Reactive blue 2 (28 microM). The last three inhibitors have similar potencies as inhibitors of ATP hydrolysis by whole parotid acinar cells. ARL67156, a selective inhibitor of ecto-ATPase, had an IC50 of approx. 120 microM. Suramin displayed non-competitive inhibition of ecto-ATPase whereas the inhibitory effects of ATPgammaS and Reactive blue 2 were curvilinear on Dixon plots. These results define the effects of various agents on ecto-ATPase in an exocrine tissue that has been shown to respond to extracellular ATP.
Dowd
F J
FJ
Department of Pharmacology, Creighton University Medical School, Omaha, NE 68178, USA. fdowd@creighton.edu
Li
L S
LS
Zeng
W
W
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006868:Hydrolysis; D007700:Kinetics; D008566:Membranes / Q000187:drug effects / Q000201:enzymology; D010306:Parotid Gland / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology
C092431:6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP; D004791:Enzyme Inhibitors; D013873:Thionucleotides; D014227:Triazines; C022571:adenosine 5'-O-(3-thiotriphosphate); C012842:Cibacron Blue F 3GA; D013498:Suramin; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C027201:ectoATPase; D000254:Sodium-Potassium-Exchanging ATPase; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; C008501:2-methylthio-ATP