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

✍ Scribed by Helge Hohage; Fritz Matzkies; Ulrike Mergelsberg; Marina Löhr; Joachim Greven

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 65 KB
• Volume: 19
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/(sici)1099-1263(199909/10)19:5<337::aid-jat585>3.0.co;2-a

✦ Synopsis

Recent work demonstrated that the heavy metal ion Cd2+ increases the transport of p-aminohippuric acid (PAH) across the basolateral membrane of microdissected non-perfused rabbit kidney S2 proximal tubule segments. Usually, such ions induce damage of various renal transport systems, therefore the effects of divalent metal ions Zn2+, Co2+ and Ni2+ on this transporter were investigated. Addition of Ni2+ or Zn2+ to the bathing solution leads to a significant reduction of basolateral PAH transport, with IC50 values of 2 x 10(-5) and 10(-6) M, respectively, whereas Co2+ failed to inhibit PAH accumulation. 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 sites. This finding is supported by the fact that thrombin abolished the cation effects.