Effects of inorganic divalent cations on the renal basolateral transport system for organic anions

Recent work demonstrated that the heavy metal ion Cd2+ increases the transp ort of p-aminohippuric acid (PAH) across the basolateral membrane of microd issected non-perfused rabbit kidney S2 proximal tubule segments. Usually, s uch ions induce damage of various renal transport systems, therefore the ef fects of divalent metal ions Zn2+, Co2+ and Ni2+ on this transporter were i nvestigated. Addition of Ni2+ or Zn2+ to the bathing solution leads to a si gnificant reduction of basolateral PAH transport, with IC50 values of 2 x 1 0(-5) and 10(-6) M, respectively, whereas Co2+ failed to inhibit PAH accumu lation. Simultaneous incubation with thrombin (10(-9) M), which is known to increase [Ca2+](i) abolished the effects of the divalent ions. Our results indicate that Ni2+ and Zn2+ reduce cellular PAH uptake. Because Ni2+ and Zn2+ are calcium channel blockers, these effects are probably due to a reduction of [Ca2+](i) by an interaction of these metals with binding sites in the calcium channel, whereas Co2+ does not affect these binding s ites. This finding is supported by the fact that thrombin abolished the cat ion effects. Copyright (C) 1999 John Wiley & Sons, Ltd.