Regulation of renal atrial natriuretic peptide receptors in pregnant sheep.
These studies were designed to characterize the atrial natriuretic peptide (ANF) receptor subtypes (guanylyl cyclase GC-A and GC-B and ANF-C) in normal sheep kidneys and to evaluate alterations in receptor kinetics during pregnancy. Kidneys were obtained from 12 nonpregnant and 12 pregnant sheep during late gestation and maintained on a 100 mmol/day salt intake. Competition binding receptor assays using [125I]human ANF showed that inner medullary membranes are exclusively of the GC-A subtype. The maximum binding capacity (Bmax, 109 +/- 12 vs. 89 +/- 18 fmol/mg protein) and dissociation constant (Kd, 240 +/- 70 vs. 324 +/- 99 pM) are not altered by pregnancy. Specific binding of glomerular membranes to [125I]Tyr-C-type natriuretic peptide, which shows the highest affinity toward GC-B receptors, was observed, but this binding was abolished when ANF-C receptors were saturated with excess C-ANF-(101-121), suggesting that [125I]Tyr-C-type natriuretic peptide binding was mediated by ANF-C receptors. Binding of [125I]human ANF to glomerular membranes revealed that glomerular ANF receptor number was reduced during pregnancy (1040 +/- 212 vs. 335 +/- 42 fmol/mg protein; P = 0.001), but binding affinity was not changed. The reduced number was mainly due to a decrease in ANF-C receptor density (832 +/- 213 vs. 260 +/- 31 fmol/mg protein; P = 0.005). Autoradiography of whole kidney frozen sections produced similar findings. These studies demonstrate that GC-B receptors are absent from renal glomeruli and inner medulla, and that ANF receptor subtypes are differentially regulated in the pregnant sheep kidney, suggesting a role for ANF in the altered volume and pressure homeostasis of pregnancy.
Mukaddam-Daher
S
S
Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada.
Gutkowska
J
J
Tremblay
J
J
Dam
T V
TV
Quillen
E W
EW
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D005260:Female; D007668:Kidney / Q000737:chemistry*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011869:Radioligand Assay; D017461:Receptors, Atrial Natriuretic Factor / Q000032:analysis*; D012756:Sheep
C080026:C-type natriuretic peptide (1-22), Tyr(0)-; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D017461:Receptors, Atrial Natriuretic Factor