Correlation between the inhibitory effects of basic drugs on the uptake of cardiac glycosides and taurocholate by isolated rat hepatocytes.
The role of the multispecific bile acid transporter for cardiac glycoside uptake is still controversial. This study was designed to examine the inhibitory effects of basic drugs (verapamil, dipyridamole, nifedipine, chlorpromazine, disopyramide, quinidine, propranolol, and lidocaine) on taurocholate uptake by isolated rat hepatocytes and to compare these effects with inhibition of ouabain uptake. Sodium-dependent taurocholate uptake was significantly reduced, to 50-70% of the control value, by 50 microM verapamil, dipyridamole, and nifedipine. Sodium-independent taurocholate uptake was more extensively inhibited, to 20-40%, by these basic drugs. The inhibition of ouabain uptake correlated better with sodium-independent taurocholate uptake (gamma = 0.918) than with sodium-dependent taurocholate uptake (gamma = 0.714). Taurocholate competitively inhibited ouabain uptake in the absence of sodium. These results indicate that the cardiac glycoside transport system is similar to the sodium-independent taurocholate transport system.
Okudaira
K
K
Division of Xenobiotic Metabolism and Disposition, National Institute of Hygienic Sciences, Tokyo, Japan.
Yamazaki
M
M
Sawada
Y
Y
Sugiyama
Y
Y
Iga
T
T
Hanano
M
M
D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology; D004206:Disopyramide / Q000494:pharmacology; D004347:Drug Interactions; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010042:Ouabain / Q000493:pharmacokinetics*; D011433:Propranolol / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000502:physiology; D013656:Taurocholic Acid / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D010042:Ouabain; D013656:Taurocholic Acid; D004176:Dipyridamole; D008012:Lidocaine; D012964:Sodium; D011433:Propranolol; D014700:Verapamil; D004206:Disopyramide; D009543:Nifedipine; D011802:Quinidine; D002746:Chlorpromazine