Distinct localization of atrial natriuretic factor and angiotensin II binding sites in the glomerulus

Abstract

A comparative study of the localization of 125I-labeled atrial natriuretic factor (ANF) and 125I-labeled angiotensin II (ANG II) binding sites in the glomerulus of the rat, after an intravascular injection, has been done by ultrastructural radioautography. 125I-ANF binding sites are localized predominantly on the podocytes of the visceral epithelium (63%) followed by the endothelium of capillaries (14%), the parietal epithelium (13%), and finally mesangial cells (10%). In a comparative study, it was confirmed that 125I-ANG II uptake is localized predominantly on mesangial cells (60%) followed by epithelial visceral cells (23%) and the endothelium of capillaries (16%). Using isolated rat glomeruli, it was confirmed that ANG II decreases glomerular size (maximum effect of 15%) with an apparent half maximum effective concentration (EC50) between 10(-9) and 10(-8) M. Although ANF alone has no apparent effect on glomerular size, it inhibits the contractile effect of ANG II with a half maximum inhibitory concentration (IC50) between 10(-11) and 10(-10) M. These results suggest that an intraglomerular mechanism other than glomerular arteriolar resistance may be involved in the modulation of glomerular filtration rate by ANF. The presence of 125I-ANF uptake mainly in foot processes of visceral epithelial cells of glomeruli in vivo and the inhibition of ANG II decrease in glomerular size by ANF in vitro raise the possibility that ANF may regulate the ultrafiltration coefficient by two mechanisms: modulation of glomerular permeability, and surface area.

Localization and Functional Properties of Angiotensin II AT1 Receptors in the Kidney. Focus on Renomedullary Interstitial Cells.

“…Although previous ultrastructural autoradiographic studies have not shown a high density of Ang II receptors in afferent and efferent arterioles after intravascular injection of 1251-Ang II (70,71,87), radioligand binding assays in isolated preglomerular resistant vessels have identified high affinity Ang II receptors in normotensive rats (88) and in spontaneously hypertensive rats (86). Binding competition studies with the subtype selective antagonists losartan and PD 123319 indicate a majority of AT1 receptors (> 80% to 90%) with a small proportion of PD 123319-sensitive AT2 sites in these isolated vascular membranes (86,88).…”

“…The cellular distribution of Ang II receptor subtypes in the glomerulus shows AT1 receptors almost exclusively in mesangial cells, but not in the cells of epithelium, basement membranes, or capillary endothelium (70)(71)(72)(73). In situ hybridization studies using an AT1 receptor riboprobe have identified AT1 receptor mRNA in rat glomeruli, presumably in mesangial cells and the vascular pole (65,68).…”

Calmodulin-dependent Protein Kinase II/cAMP Response Element-binding Protein/Wnt/β-Catenin Signaling Cascade Regulates Angiotensin II-induced Podocyte Injury and Albuminuria

“…Podocytes express both AT1 and AT2 receptors that provide high-affinity binding sites for Ang II (7)(8)(9)(10)(11)(12)(13). Administration of exogenous Ang II or targeted overexpression of AT1 to glomerular podocytes resulted in albuminuria and focal segmental glomerular sclerosis in mice (4,8,14,15).…”

Atrial natriuretic factor effects on cyclic nucleotides in a human renal cell line.

“…9 This observation provides biochemical support for the renal cellular nature of the Wilms' tumor, which is characterized histologically by the presence of preglomerular and pretubular structures 10 and therefore should have contained ANF responsive cells. 4 - 7 The hKT cells depicted in Figure 1 show a spherical epithelial morphology comparable with that depicted for the parent cell line SK-NEP-1. 9 Taken together, the data in the present report suggest that this Wilms' tumor cell line possesses cells that exhibit properties expected of ANF responsive target cells, and thus this cell line may serve as a useful in vitro model for investigating ANF-mediated events at a cellular level.…”

“…The most likely second messenger for ANF is cyclic guanosine monophosphate (cGMP). 3 Either ANF binding or stimulation of cGMP formation has been demonstrated in a variety of renal structures including glomerular visceral podocytes, 4 capillary endothelial cells, 4 mesangial cells, 5 cells of the cortical collecting tubule, 6 and juxtaglomerular cells. 7 Increased cGMP accumulation results from ANF stimulation of a membrane-associated guanylate cyclase 3 although ANF inhibition of adenylate cyclase has also been reported.…”