Transporters involved in renal excretion of N-carbamoylglutamate, an orphan drug to treat inborn N-acetylglutamate synthase deficiency.

Transporters involved in renal excretion of N-carbamoylglutamate, an orphan drug to treat inborn N-acetylglutamate synthase deficiency. Am J Physiol Renal Physiol. 2014 Oct 29;:ajprenal.00482.2014 Authors: Schwob E, Hagos Y, Burckhardt G, Burckhardt BC Abstract Inborn defects in the N-acetylglutamate synthase (NAGS) cause a reduction of N-acetylglutamate (NAG), an essential cofactor for the initiation of the urea cycle. As a consequence, blood ammonium concentrations are elevated, leading to severe neurological disorders. The orphan drug, N-carbamoylglutamate (NCG; carbaglu®), efficiently overcomes NAGS deficiency. However, not much is known about the transporters involved in uptake, distribution, and elimination of the divalent organic anion NCG. Organic anion transporting-polypeptides (OATPs) as well as organic anion transporters (OATs) working in cooperation with the sodium dicarboxylate co-transporter 3 (NaDC3) accept a wide variety of structurally unrelated drugs. To test for possible interactions with OATPs and OATs, the impact of NCG on these transporters stably transfected in HEK293 cells was measured. The two-electrode voltage clamp technique was used to monitor NCG-mediated currents in Xenopus laevis oocytes expressing NaDC3. Neither the OATPs nor OAT2 and OAT3 interacted with NCG, but OAT1 transported NCG. In addition, NCG was identified as a high affinity substrate of NaDC3. Pre-incubation of OAT4-transfected HEK293 cells with NCG showed ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research

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Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
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Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
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Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
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Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
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