Evidence for particulate guanylate cyclase in rat kidney after stimulation by atrial natriuretic factor. An ultracytochemical study

1990 ◽  
Vol 22 (9) ◽  
pp. 469-474 ◽  
Author(s):  
M. G. Rambotti ◽  
C. Saccardi ◽  
A. Spreca
1992 ◽  
Vol 263 (5) ◽  
pp. F974-F978
Author(s):  
J. E. Greenwald ◽  
D. Ritter ◽  
E. Tetens ◽  
P. S. Rotwein

To date, atrial natriuretic factor (ANF) mRNA has eluded detection in the mammalian kidney, although we and others have identified ANF protein in the kidney using immunohistochemical and immunoassay techniques. Furthermore, we have demonstrated the synthesis and secretion of the ANF prohormone in the distal cortical nephron of the intact rat kidney and from rat primary cultured renal distal cortical tubular epithelial cells. In the present study, we show that the ANF gene is expressed in the kidney. Amplification of RNA isolated from rat distal cortical tubular epithelial cultures using ANF specific primers produced a 213-bp fragment that specifically hybridized to a 32P-labeled ANF cDNA. We had previously demonstrated these cultures to be enriched for the renal ANF synthetic and secretory cell type. However, we were unable to detect an ANF gene transcript in total rat kidney RNA using the above-mentioned polymerase chain reaction (PCR) conditions. Reanalysis of normal rat kidney PCR products by a second round of PCR amplification using nested primers successfully identified ANF mRNA. Similar to cultured kidney epithelial cells, normal rat kidney expresses ANF mRNA, but at a very low abundance, thus necessitating two rounds of PCR amplification. Further characterization of rat cortical distal tubular epithelia poly(A)+ RNA by Northern analysis revealed two ANF gene transcripts. A 1.0-kb message that comigrated with rat atrial ANF mRNA, and a second larger 1.4-kb transcript. These studies further substantiate the synthesis of ANF in the mammalian kidney. Unlike the mammalian heart, the kidney contains two ANF gene transcripts.


1992 ◽  
Vol 282 (2) ◽  
pp. 533-537 ◽  
Author(s):  
R M Goraczniak ◽  
T Duda ◽  
R K Sharma

Atrial natriuretic factor (ANF)-dependent guanylate cyclase is a single-chain transmembrane-spanning protein, containing an ANF receptor and having catalytic activity. ANF binding to the receptor domain activates the catalytic domain, generating the second messenger cyclic GMP. Obligatory in this activation process is an intervening step regulated by ATP, but its mechanism is not known. Through a programme of site-directed and deletion mutagenesis/expression studies, we report herein the identity of a structural motif (Gly503-Arg-Gly-Ser-Asn-Tyr-Gly509) that binds ATP and amplifies the ANF-dependent cyclase activity; this, therefore, represents an ATP-regulatory module (ARM) of the enzyme, which plays a pivotal role in ANF signalling.


1995 ◽  
Vol 27 (2) ◽  
pp. 233-240 ◽  
Author(s):  
S. Tei ◽  
D. Vagnetti ◽  
T. Secca ◽  
B. Santarella ◽  
C. Roscani ◽  
...  

FEBS Letters ◽  
1985 ◽  
Vol 189 (1) ◽  
pp. 8-12 ◽  
Author(s):  
Nicole Ardaillou ◽  
Marie-Paule Nivez ◽  
Raymond Ardaillou

1989 ◽  
Vol 67 (9) ◽  
pp. 1124-1129 ◽  
Author(s):  
Johanne Tremblay ◽  
Pavel Hamet

Since atrial natriuretic factor (ANF) is a natriuretic and vasodilatory hormone, its mechanisms of action expectedly involve so-called negative pathways of cell stimulation, notably cyclic nucleotides. Indeed, the guanylate cyclase–cyclic GMP (cGMP) system appears to be the principal mediator of ANF's action. Specifically, particulate guanylate cyclase, a membrane glycoprotein, transmits ANF's effects, as opposed to the activation of soluble guanylate cyclase by such agents as sodium nitroprusside. The stimulation of particulate guanylate cyclase by ANF manifests several characteristics. One of them is the functional irreversibility of stimulation with its apparent physiological consequences: the extended impact of ANF on diuresis and vasodilation in vivo lasts beyond the duration of increased plasma ANF levels and is accompanied by a prolonged elevation of cGMP. Another characteristic is the parallelism between guanylate cyclase stimulation and increases of cGMP in extracellular fluids. cGMP egression appears to be an active process, yet its physiological implications remain to be uncovered. In heart failure, cGMP continues to reflect augmented ANF levels, suggesting that in this disease, the lack of an ANF effect on sodium excretion is due to a defect distal to cGMP generation. In hypertension, where ANF levels are either normal or slightly elevated, probably secondary to high blood pressure, the ANF responsiveness of the particulate guanylate cyclase–cGMP system, the hypotensive effects, diuresis and natriuresis are exaggerated. The implications of this exaggerated responsiveness of the ANF–cGMP system in the pathophysiology of hypertension and its potential therapeutic connotations remain to be evaluated.Key words: ANF, cGMP, guanylate cyclase, hypertension, heart failure.


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