Functional characterization of the basolateral rat liver organic anion transporting polypeptide.
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Kullak-Ublick GA, Hagenbuch B, Stieger B, Wolkoff AW, Meier PJ
Functional characterization of the basolateral rat liver organic anion transporting polypeptide.
Hepatology. 1994 Aug;20(2):411-6.
- PubMed ID
- 8045503 [ View in PubMed]
- Abstract
To characterize the transport functions of a recently cloned basolateral organic anion transporting polypeptide of rat hepatocytes we performed further kinetic transport and substrate cis-inhibition studies in organic anion-transporting polypeptide-cRNA injected Xenopus laevis oocytes. The studies demonstrate saturable Na(+)-independent sulfobromophthalein (Michaelis-Menten constant, 1.5 mumol/L) and taurocholate (Michaelis-Menten constant, 50 mumol/L) uptake by organic anion-transporting polypeptide. Sulfobromophthalein uptake was inhibited by the following organic anions: 0.01 mmol/L bilirubin (43%), 0.1 mmol/L indocyanine green (81%), 0.1 mmol/L 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS; 52%) and 1 mmol/L probenecid (74%). Competitive inhibition was shown for indocyanine green (inhibition constant about 1.3 mumol/L). Sulfobromophthalein and taurocholate uptakes were also inhibited by cholate, chenodeoxycholate, deoxycholate and ursodeoxycholate, as well as their glycine and taurine conjugates. Organic anion-transporting polypeptide also mediated uptake of glycocholate, tauroursodeoxycholate and taurochenodeoxycholate. No cis-inhibition of sulfobromophthalein uptake was seen in the presence of ATP, para-aminohippuric acid, bumetanide, digitoxin, reduced glutathione, leukotriene C4, nicotinic acid, ouabain, oxalate, rifampicin, succinate or sulfate. Furthermore, radioactively labeled para-aminohippuric acid, alpha-ketoglutarate and reduced glutathione were not taken up by organic anion-transporting polypeptide in cRNA-injected frog oocytes. These data confirm that organic anion-transporting polypeptide represents a novel hepatocellular organic anion uptake system that can mediate Na(+)-independent transport of monovalent (e.g., bile acids) and divalent (e.g., sulfobromophthalein and indocyanine green) cholephilic organic anions.(ABSTRACT TRUNCATED AT 250 WORDS)
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Cholic Acid Solute carrier organic anion transporter family member 1A2 Protein Humans UnknownSubstrateInhibitorInducerDetails Deoxycholic acid Solute carrier organic anion transporter family member 1A2 Protein Humans UnknownSubstrateInhibitorDetails Glycochenodeoxycholic Acid Solute carrier organic anion transporter family member 1A2 Protein Humans UnknownSubstrateInhibitorDetails Probenecid Solute carrier organic anion transporter family member 1A2 Protein Humans UnknownInhibitorDetails Taurocholic acid Solute carrier organic anion transporter family member 1A2 Protein Humans UnknownSubstrateInhibitorInducerDetails Ursodeoxycholic acid Solute carrier organic anion transporter family member 1A2 Protein Humans UnknownSubstrateInhibitorInducerDetails