VASOPRESSIN-ELICITED WATER AND UREA PERMEABILITIES ARE ALTERED IN IMCD IN HYPERCALCEMIC RATS

To investigate how hypercalcemia blunts renal concentrating ability, a lterations in basal and arginine vasopressin (AVP)-elicited osmotic wa ter (P-f) and urea (P-urea) permeabilities were measured in isolated p erfused terminal inner medullary collecting duets (IMCD) from control and chronically hypercalcemic rats after dihydrotachysterol (DHT) (M. Levi, L. Peterson, and T. Berl. Kidney Int. 23: 489-497, 1983) treatme nt. The IMCD P-f of DHT-treated rats did not increase significantly af ter AVP and was accompanied by a significant 87 +/- 4% reduction in aq uaporin-2 (AQP-2) protein but not mRNA. In contrast, both basal and AV P-elicited IMCD P-urea 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/polyval ent cation-sensing receptor protein (CaR) antiserum revealed specific alterations in CaR bands in endosomes purified from the apical membran es of inner medulla of DHT rats. These data are the first detailed ana lyses of hypercalcemia-induced alterations in AVP-regulated permeabili ties and membrane transporters in IMCD. We conclude that selective alt erations in IMCD transport occur in hypercalcemia, permitting the body to dispose of excess calcium without forming calcium-containing renal stones.