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 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.
Hohage
H
H
Medical Department of D, University of Münster, Germany. hohage@uni-muenster.de
Matzkies
F
F
Mergelsberg
U
U
Löhr
M
M
Greven
J
J
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002413:Cations, Divalent / Q000494:pharmacology*; D003035:Cobalt / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D009532:Nickel / Q000494:pharmacology; D011817:Rabbits; D013917:Thrombin / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics*
D002413:Cations, Divalent; D003035:Cobalt; D009532:Nickel; D013917:Thrombin; D015032:Zinc; D010130:p-Aminohippuric Acid