POLARIZED DISTRIBUTION OF RENAL NATRIURETIC PEPTIDE RECEPTORS IN NORMAL PHYSIOLOGY AND ISCHEMIA

The polarized expression of guanylyl cyclase-coupled natriuretic pepti de receptors, types A (GC-A) and B (GC-B), was measured in inner medul lary collecting ducts (IMCD) of normal and ischemic rat kidneys, as we ll as in IMCD cells. Exposure of normal rat kidney medulla to an anti- GC-A antibody demonstrated a propensity of receptor staining on the ce llular basal membrane. The polarization of GC-A receptors was lost in the ischemic kidney. The maximal binding capacity of I-125-atrial natr iuretic factor (ANF) to the basal membrane of the inner medullary cell line mIMCD-K2 was five times greater than that to the apical membrane . ANF or C-type natriuretic peptide (CNP) added to the basal side of c ultured cells resulted in guanosine 3',5'-cyclic monophosphate formati on that was greater than when applied to the apical side. Depletion of ATP stores in cultured cells was followed by an increase of I-125-ANF binding to apical cellular membranes. Similar results were obtained w hen receptor guanylyl cyclase activity was assayed. In conclusion, the se results suggest that functional GC-A and GC-B receptors are present predominantly on the basal membrane of IMCD. However, depletion of ce llular ATP stores such as in ischemia is followed by a partial loss of polarization.