Competitive inhibition of renal transport of p-aminohippurate by analogues of chlorothiazide

¹ Department of Medicine, College of Physicians and Surgeons, Columbia University; Presbyterian Hospital, New York City; Department of Medicine, Harvard Medical School; and Massachusetts General Hospital, Boston, Massachusetts

Competitive inhibition of p-aminohippurate (PAH) transport by analogues of chlorothiazide has been demonstrated with slices of rabbit kidney cortex. Although analogues of low pK₁ are better inhibitors of PAH transport than are analogues of higher pK₁, no clear dependence of inhibitory capacity on degree of ionization at physiological values of pH was demonstrable. In contrast to earlier findings with phenolsulfonphthaleins and m- and p-substituted hippurates, no relation was noted between rate of transport and molecular weight or capacity to inhibit PAH transport. Similarly, no relation was noted between rate of transport and pK₁. None of the analogues affected potassium content or uptake of K⁴².