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Effects of inorganic divalent cations on the renal basolateral transport system for organic anions
Author(s) -
Hohage Helge,
Matzkies Fritz,
Mergelsberg Ulrike,
Löhr Marina,
Greven Joachim
Publication year - 1999
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/(sici)1099-1263(199909/10)19:5<337::aid-jat585>3.0.co;2-a
Subject(s) - chemistry , divalent , calcium , inorganic chemistry , biophysics , metal , epithelial polarity , membrane , biochemistry , organic chemistry , biology
Recent work demonstrated that the heavy metal ion Cd 2+ 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 Zn 2+ , Co 2+ and Ni 2+ on this transporter were investigated. Addition of Ni 2+ or Zn 2+ to the bathing solution leads to a significant reduction of basolateral PAH transport, with ic 50 values of 2 × 10 −5 and 10 −6 M, respectively, whereas Co 2+ failed to inhibit PAH accumulation. Simultaneous incubation with thrombin (10 −9 M), which is known to increase [Ca 2+ ] i , abolished the effects of the divalent ions. Our results indicate that Ni 2+ and Zn 2+ reduce cellular PAH uptake. Because Ni 2+ and Zn 2+ are calcium channel blockers, these effects are probably due to a reduction of [Ca 2+ ] i by an interaction of these metals with binding sites in the calcium channel, whereas Co 2+ does not affect these binding sites. This finding is supported by the fact that thrombin abolished the cation effects. Copyright © 1999 John Wiley & Sons, Ltd.