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Involvement of an organic anion transporter (canalicular multispecific organic anion transporter/multidrug resistance-associated protein 2) in gastrointestinal secretion of glutathione conjugates in rats.
J Pharmacol Exp Ther. 2000 Jan; 292(1):433-9.JP

Abstract

We investigated the role of cMOAT/MRP2 (canalicular multispecific organic anion transporter/multidrug resistance-associated protein 2) in the intestinal secretion of organic anions by comparing the behavior in Sprague-Dawley (SD) rats and Eisai hyperbilirubinemic rat (EHBR) whose cMOAT/MRP2 is hereditarily defective. After i.v. administration of 1-chloro-2,4-dinitrobenzene (30 micromol/kg), the biliary and intestinal excretion of its glutathione conjugate 2, 4-dinitrophenyl-S-glutathione (DNP-SG), a substrate for cMOAT/MRP2, was significantly reduced in EHBR compared with SD rats. This result also was confirmed by Ussing chamber studies; DNP-SG showed 1.5-fold greater serosal-to-mucosal flux compared with the mucosal-to-serosal flux in SD rats, whereas a similar flux was observed in both directions in EHBR. In addition, metabolic inhibitors reduced the preferential serosal-to-mucosal flux of DNP-SG in SD rats. In everted sac studies, intestinal secretion clearance, defined as the efflux rate of DNP-SG into the mucosal side divided by the area under the curve on the serosal side, was significantly lower in the jejunum of EHBR than that in SD rats. Northern blot analyses demonstrated the highest mRNA level of cMOAT/MRP2 in the jejunum, which is in good agreement with the results of the everted sac studies. These results suggest that cMOAT/MRP2 is involved in the secretion of organic anions in the small intestine.

Authors+Show Affiliations

Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

10604980

Citation

Gotoh, Y, et al. "Involvement of an Organic Anion Transporter (canalicular Multispecific Organic Anion Transporter/multidrug Resistance-associated Protein 2) in Gastrointestinal Secretion of Glutathione Conjugates in Rats." The Journal of Pharmacology and Experimental Therapeutics, vol. 292, no. 1, 2000, pp. 433-9.
Gotoh Y, Suzuki H, Kinoshita S, et al. Involvement of an organic anion transporter (canalicular multispecific organic anion transporter/multidrug resistance-associated protein 2) in gastrointestinal secretion of glutathione conjugates in rats. J Pharmacol Exp Ther. 2000;292(1):433-9.
Gotoh, Y., Suzuki, H., Kinoshita, S., Hirohashi, T., Kato, Y., & Sugiyama, Y. (2000). Involvement of an organic anion transporter (canalicular multispecific organic anion transporter/multidrug resistance-associated protein 2) in gastrointestinal secretion of glutathione conjugates in rats. The Journal of Pharmacology and Experimental Therapeutics, 292(1), 433-9.
Gotoh Y, et al. Involvement of an Organic Anion Transporter (canalicular Multispecific Organic Anion Transporter/multidrug Resistance-associated Protein 2) in Gastrointestinal Secretion of Glutathione Conjugates in Rats. J Pharmacol Exp Ther. 2000;292(1):433-9. PubMed PMID: 10604980.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of an organic anion transporter (canalicular multispecific organic anion transporter/multidrug resistance-associated protein 2) in gastrointestinal secretion of glutathione conjugates in rats. AU - Gotoh,Y, AU - Suzuki,H, AU - Kinoshita,S, AU - Hirohashi,T, AU - Kato,Y, AU - Sugiyama,Y, PY - 1999/12/22/pubmed PY - 1999/12/22/medline PY - 1999/12/22/entrez SP - 433 EP - 9 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 292 IS - 1 N2 - We investigated the role of cMOAT/MRP2 (canalicular multispecific organic anion transporter/multidrug resistance-associated protein 2) in the intestinal secretion of organic anions by comparing the behavior in Sprague-Dawley (SD) rats and Eisai hyperbilirubinemic rat (EHBR) whose cMOAT/MRP2 is hereditarily defective. After i.v. administration of 1-chloro-2,4-dinitrobenzene (30 micromol/kg), the biliary and intestinal excretion of its glutathione conjugate 2, 4-dinitrophenyl-S-glutathione (DNP-SG), a substrate for cMOAT/MRP2, was significantly reduced in EHBR compared with SD rats. This result also was confirmed by Ussing chamber studies; DNP-SG showed 1.5-fold greater serosal-to-mucosal flux compared with the mucosal-to-serosal flux in SD rats, whereas a similar flux was observed in both directions in EHBR. In addition, metabolic inhibitors reduced the preferential serosal-to-mucosal flux of DNP-SG in SD rats. In everted sac studies, intestinal secretion clearance, defined as the efflux rate of DNP-SG into the mucosal side divided by the area under the curve on the serosal side, was significantly lower in the jejunum of EHBR than that in SD rats. Northern blot analyses demonstrated the highest mRNA level of cMOAT/MRP2 in the jejunum, which is in good agreement with the results of the everted sac studies. These results suggest that cMOAT/MRP2 is involved in the secretion of organic anions in the small intestine. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/10604980/Involvement_of_an_organic_anion_transporter__canalicular_multispecific_organic_anion_transporter/multidrug_resistance_associated_protein_2__in_gastrointestinal_secretion_of_glutathione_conjugates_in_rats_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10604980 DB - PRIME DP - Unbound Medicine ER -