The prostaglandin antagonist polyphloretin phosphate behaves as a nonspecific inhibitor of rat hepatic adenylate cyclase.
The mechanism of the nonspecific inhibitory effects of the prostaglandin antagonist polyphloretin phosphate (PPP) was studied on a partially purified adenylate cyclase preparation from rat livers, PPP in concentrations above 100 micrograms/ml reduced the enzyme activity below basal values regardless of the stimulator used. The activity of adenylate cyclase in a persistent active state due to enzyme preincubation with guanylylimidodiphosphate (Gpp(NH)p) was inhibited 5-10 times more weakly. Kinetic studies indicate that PPP does not influence directly the catalytic site for ATP. PPP seems to produce permanent enzyme inhibition which is not antagonized by repeated washing ot the enzyme preparation. The reduced catalytic activity of adenylate cyclase retains after treatment with PPP the character of its responsiveness to the stimulators, which depends on the state of the enzyme before exposure to the inhibitor.
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D005934:Glucagon / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D010693:Phloretin / Q000031:analogs & derivatives*; D011121:Polyphloretin Phosphate / Q000494:pharmacology*; D051381:Rats; D012969:Sodium Fluoride / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D006165:Guanylyl Imidodiphosphate; D012969:Sodium Fluoride; D005934:Glucagon; D011121:Polyphloretin Phosphate; D000262:Adenylyl Cyclases; D010693:Phloretin