ISSN:
1432-1912
Schlagwort(e):
p-Aminohippurate
;
Benzoates
;
Isolated membrane vesicles
;
Organic anion transport
;
Dog kidney
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Summary The effect of substituted benzoates on the transport of p-aminohippurate (PAH) was studied in basolateral (BLMV) and brush border membrane vesicles (BBMV) isolated from dog kidney cortex. For both membranes, kinetic analysis of [3H]PAH transport in the presence of a fixed concentration of two different benzoates, respectively, revealed an increase in the apparent K m, for PAH, while the transport capacity (V max) was unaffected. This is compatible with competitive inhibition of a common transport pathway. A range of 19 monosubstituted benzoates were then tested as potential inhibitors by measuring the probenecid-sensitive fraction of 100 μmol/l PAH uptake into BLMV and BBMV in the presence of 5 mmol/l benzoate, and apparent inhibition constants (K j) were calculated. For all benzoates the inhibitory potency in BBMV was lower than in BLMV, but the pattern of inhibition was similar; the most pronounced inhibition was found for 3-Cl- and 4-Cl-benzoate, while the least pronounced inhibition was found for the 3-NH2 and 4-NH2 substitutes. The inhibitory potency, expressed as logK i, correlated significantly with the relative hydrophobicity of the benzoates determined by reversed phase HPLC, whereas a poor correlation was found between pKa and logK i. This indicates that hydrophobic and electronic parameters are the main determinants of affinity for the PAH transport system. It is suggested that the PAH transport system present in the proximal tubules is responsible for the active secretion of benzoates by the mammalian kidney.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF00180684
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