Polarized distribution of renal natriuretic peptide receptors in normal physiology and ischemia.
The polarized expression of guanylyl cyclase-coupled natriuretic peptide receptors, types A (GC-A) and B (GC-B), was measured in inner medullary collecting ducts (IMCD) of normal and ischemic rat kidneys, as well as in IMCD cells. Exposure of normal rat kidney medulla to an anti-GC-A antibody demonstrated a propensity of receptor staining on the cellular basal membrane. The polarization of GC-A receptors was lost in the ischemic kidney. The maximal binding capacity of 125I-atrial natriuretic 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 cultured cells resulted in guanosine 3',5'-cyclic monophosphate formation that was greater than when applied to the apical side. Depletion of ATP stores in cultured cells was followed by an increase of 125I-ANF binding to apical cellular membranes. Similar results were obtained when receptor guanylyl cyclase activity was assayed. In conclusion, these results suggest that functional GC-A and GC-B receptors are present predominantly on the basal membrane of IMCD. However, depletion of cellular ATP stores such as in ischemia is followed by a partial loss of polarization.
Ritter
D
D
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Dean
A D
AD
Guan
Z H
ZH
Greenwald
J E
JE
D000818:Animals; D002460:Cell Line; D016764:Cell Polarity; D006162:Guanylate Cyclase / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D045283:Natriuretic Agents / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012016:Reference Values; D012079:Renal Circulation; D014018:Tissue Distribution
D045283:Natriuretic Agents; D011956:Receptors, Cell Surface; D006162:Guanylate Cyclase