title: Differential calcium transport disturbances in renal membrane vesicles after cadmium-metallothionein injection in rats.
abstract: Cadmium-metallothionein (CdMT) induced calciuria may result from disturbed calcium (Ca) transport through the renal tubular epithelium. The present study aimed at defining time of onset and the degree of disturbed calcium transport. Kidneys were obtained from rats at 4, 12 and 24 h after a single injection of CdMT (dose 0.4 mg Cd/kg b.w.), and compared to saline injected controls. Rapid-filtration 45Ca-assays were performed on basolateral and luminal membrane vesicles, isolated from kidney cortex using a sequential ultracentrifugation procedure. Luminal 45Ca uptake was increased at 4 h and then declined to about 80% of controls, suggesting an early phase perturbation of Ca absorption. Basolateral 45Ca uptake was reduced to less than 50% of controls, starting already at 4 h while 45Ca binding was reduced at 8 h. This may reflect an inhibited basolateral Ca pump mechanism after the binding step. Since the Ca pump normally expels Ca from the cell, an accumulation of intracellular calcium was indicated. Metal analysis verified a four-fold increase of Ca in kidney cortex at 24 h. This suggests that Cd impact on tubular cells involves disturbances on cellular absorption as well as expulsion of Ca.
authors.affiliation: Department of Occupational and Environmental Medicine, Umeå University, Sweden. per.leffler@bmg.umu.se
authors.forename: P E
authors.initials: PE
authors.lastname: Leffler
authors.forename: T
authors.initials: T
authors.lastname: Jin
authors.forename: G F
authors.initials: GF
authors.lastname: Nordberg
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002132:Calcium Radioisotopes; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013054:Spectrophotometry, Atomic
chemical_list: D015220:Calcium Channels; D002132:Calcium Radioisotopes; C004203:cadmium-binding protein; D000255:Adenosine Triphosphate; D008668:Metallothionein; D002118:Calcium