title: Vasopressin-elicited water and urea permeabilities are altered in IMCD in hypercalcemic rats.
abstract: To investigate how hypercalcemia blunts renal concentrating ability, alterations in basal and arginine vasopressin (AVP)-elicited osmotic water (Pf) and urea (Purea) permeabilities were measured in isolated perfused terminal inner medullary collecting ducts (IMCD) from control and chronically hypercalcemic rats after dihydrotachysterol (DHT) (M. Levi, L. Peterson, and T. Berl. Kidney Int. 23: 489-497, 1983) treatment. The IMCD Pf of DHT-treated rats did not increase significantly after AVP and was accompanied by a significant 87 +/- 4% reduction in aquaporin-2 (AQP-2) protein but not mRNA. In contrast, both basal and AVP-elicited IMCD Purea from DHT rats were significantly increased and accompanied by a significant 41 +/- 11% increase in AVP-regulated urea transporter protein content. Immunoblotting with anti-calcium/polyvalent cation-sensing receptor protein (CaR) antiserum revealed specific alterations in CaR bands in endosomes purified from the apical membranes of inner medulla of DHT rats. These data are the first detailed analyses of hypercalcemia-induced alterations in AVP-regulated permeabilities and membrane transporters in IMCD. We conclude that selective alterations in IMCD transport occur in hypercalcemia, permitting the body to dispose of excess calcium without forming calcium-containing renal stones.
authors.affiliation: Renal Division, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Sands
authors.forename: F X
authors.initials: FX
authors.lastname: Flores
authors.forename: A
authors.initials: A
authors.lastname: Kato
authors.forename: M A
authors.initials: MA
authors.lastname: Baum
authors.forename: E M
authors.initials: EM
authors.lastname: Brown
authors.forename: D T
authors.initials: DT
authors.lastname: Ward
authors.forename: S C
authors.initials: SC
authors.lastname: Hebert
authors.forename: H W
authors.initials: HW
authors.lastname: Harris
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D005919:Glomerular Filtration Rate; D006934:Hypercalcemia / Q000378:metabolism* / Q000503:physiopathology*; D007679:Kidney Medulla / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000502:physiology*; D014508:Urea / Q000378:metabolism*; D014667:Vasopressins / Q000502:physiology*; D014867:Water / Q000378:metabolism*
chemical_list: D017483:Receptors, Vasopressin; D014867:Water; D014667:Vasopressins; D014508:Urea; D002118:Calcium