The binding of benzylpenicillin (PCG) to human renal cytosol and glutathione S-transferases (GST) were investigated using the centrifuge column procedure to clarify the role of renal GST in transporting PCG through the renal proximal tubule. PCG bound to the cytosol dose-dependently, and the binding was inhibited by phenolsulfonphthalein (PSP), probenecid and
p-aminosalicylic acid (PAS). PCG also bound to the GST, including the acidic GST characteristic to the kidney, and the binding was inhibited by PSP and probenecid. The organic anions and some β-lactam antimicrobial agents inhibited renal GST activity. The inhibition constants (Ki) were 0.23 for PSP, 0.93 for probenecid, 7.7 for PAS, 2.3.6 for
p-aminohippuric acid (PAH), 1.98 for cefuzonam (CZON), 14.0 for flomoxef (FMOX), 15.4 for methicillin (DMPPC), 19.2 for imipenem (IPM), 21.5 for ceftriaxone (CTRX) and 28.0 mM for PCG. Gentamicin (GM), erythromycin (EM) and fosfomycin (F0M), which are not excreted by the renal proximal tubule, showed no inhibitory effects on GST activity. It is suggested that the human renal GST plays an important role as intracellular carrier proteins for transporting organic anions and some β-lactam antimicrobial agents through the renal proximal tubule.
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