Synthetic heteroprostanoids of A- and E-types as novel non-comprehensive inhibitors of adenylyl cyclase in rat hepatocytes.
Treatment of rat hepatocyte plasma membranes with five novel synthetic heteroprostanoids of A- and E-types significantly decreased basal activity of adenylyl cyclase. Inhibition of forskolin-stimulated activity of the enzyme was seen as well. The maximal effective concentration for all substances tested was found at approximately 5x10(-6)-1x10(-5) M. The values of half maximal concentration (IC50) for all prostanoids were at the region of 0.7-1.1 microM. Prostanoids belonging to cyclopentenone group A (U-39, U-26) were less active than analogs of 11-deoxy-PGE1 (TA-227, TA-280, and TA-239). The strongest inhibitory effect of adenylyl cyclase activity (more than 3 times) was determined in the presence of prostanoid TA-227 possessing hydrophobic 15-phenyl ring and isoxazol group in omega-chain. The investigation of AC activity in the presence of different concentrations of prostanoids and varying concentrations of Mg x ATP has demonstrated that a non-comprehensive mechanism with particular effect takes place in case of AC inhibition by the heteroprostanoids.
Hubich
A I
AI
Belarussian State University, Minsk, Belarus. Hubich_Oksana@tut.by
Zheldakova
T A
TA
Chernikhova
T V
TV
Koroleva
E V
EV
Lakhvich
F A
FA
Sholukh
M V
MV
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000527:Alprostadil / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D005576:Colforsin / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008297:Male; D008956:Models, Chemical; D011453:Prostaglandins / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000067956:Adenylyl Cyclase Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000527:Alprostadil; C034008:11-deoxyprostaglandin E1