Ubiquitous and bifunctional 180 kDa atrial natriuretic factor-dependent guanylate cyclase

1991 ◽  
Vol 100 (1) ◽  
Author(s):  
RaviB. Marala ◽  
RameshwarK. Sharma
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.


1990 ◽  
Vol 22 ◽  
pp. S93
Author(s):  
Paolo Di Nardo ◽  
Marilena Minieri ◽  
Daniela Vagnetti ◽  
Daniela Carbonari ◽  
Giuseppe Peruzzi ◽  
...  

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