title: Role of Multidrug-Resistance Protein 2 in coproporphyrin transport: results from experimental studies in bile fistula rat models.
abstract: Coproporphyrin (CP) is one of the main by-products of heme biosynthesis and its abnormal accumulation is associated with different forms of porphyria. Indirect data obtained from animal and human models have suggested a possible role for Multidrug Resistance-associated Protein 2 (MRP2) and other MRPs in hepatocyte excretion of CP. Using normal, MRP2-deficient and a cholestatic rat model, we have assessed the role of MRPs in CP disposition. MRP levels were assayed using immunofluorescence. Biliary and urinary excretion patterns of CP and conjugate bilirubin were measured during equimolar infusions of CP isomers with and without phenoldibromopthalein sulfonate (BSP), a well-known MRP2 substrate. Our results suggest a role for the MRP system as a possible regulator of CP traffic and accumulation in normal and pathological conditions. Alteration in this systems (as observed in cholestatic disease) may play an important role in triggering clinical expression of porphyria in individuals with underlying mutations leading to porphyrin accumulation and may help explain the phenotypic heterogeneity in patients affected by different forms of porphyrias.
authors: Department of Medicines and Medical Specialities, University of Modena and Reggio Emilia, Italy.
authors: V
authors: V
authors: Moriondo
authors: S
authors: S
authors: Marchini
authors: P
authors: P
authors: Di Gangi
authors: M C
authors: MC
authors: Ferrari
authors: F
authors: F
authors: Nascimbeni
authors: E
authors: E
authors: Rocchi
authors: P
authors: P
authors: Ventura
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000378:metabolism*; D001663:Bilirubin / Q000652:urine; D001692:Biological Transport; D002779:Cholestasis / Q000378:metabolism / Q000473:pathology; D003306:Coproporphyrins / Q000378:metabolism* / Q000652:urine; D004195:Disease Models, Animal; D007536:Isomerism; D007566:Jaundice, Chronic Idiopathic / Q000378:metabolism / Q000473:pathology; D008297:Male; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018528:ATP-Binding Cassette Transporters; D001663:Bilirubin; D003306:Coproporphyrins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C000715087:ABCC2 protein, human; C423013:Abcc2 protein, rat; C421109:multidrug resistance-associated protein 1