Structure, Regulation, and Function of Mammalian Membrane Guanylyl Cyclase Receptors, With a Focus on Guanylyl Cyclase-A

Kühn, Michaela

doi:10.1161/01.res.0000094745.28948.4d

Cited by 239 publications

(172 citation statements)

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“…73,74 Ligand-induced NPR-A and NPR-B activation generates cGMP in target cells which in turn activates signal transduction elements such as low-and high-affinity cGMP-dependent protein kinases (PKGs). 75 NPR-C, which has a short cytoplasmic domain without GC activity, influences plasma natriuretic peptide levels and ANP half-life and acts systemically to control natriuresis and blood pressure. Although some mechanisms of action mediated by NPR-C remain unclear, it is recognized that NPR-C acts as a clearance receptor which allows the activity of the NP system to be tailored to specific local needs.…”

Section: Natriuretic Peptide Receptorsmentioning

confidence: 99%

An Unsuspected Metabolic Role for Atrial Natriuretic Peptides

Lafontan

Moro

Sengenès

et al. 2005

ATVB

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Abstract-In normal and obese humans, lipid mobilization and systemic nonesterified fatty acid levels are thought to be acutely controlled by catecholamines (ie, epinephrine and norepinephrine) and insulin. Natriuretic peptides (NPs) are known to play a key role in the regulation of salt and water balance and blood pressure homeostasis. They are involved in the pathophysiology of hypertension and heart failure. (ATP III). The NCEP definition of the metabolic syndrome includes 3 or more of the following: abdominal obesity, defined as waist circumference Ն102 cm in men and Ͼ88 cm in women; elevated triglyceride concentration Ն150 mg/dL, low HDL cholesterol (Ͻ40 mg/dL in men and Ͻ50 mg/dL in women); elevated fasting plasma glucose level (Ն110 mg/dL); and elevated blood pressure (Ն130/85 mm Hg). 1 The presence of abdominal obesity is more closely associated with the metabolic risk factors than body mass index. The prevalence of the metabolic syndrome increases with age. Obesity interferes with many metabolic pathways which underlie numerous potential risk factors. It is very difficult to differentiate between the major and minor factors, and some remain to be discovered. 2 This complexity leaves the area open and challenges basic and clinical researchers to uncover novel metabolic pathways. The discovery that cardiac natriuretic peptides (NPs) control human fat cell function is a provocative observation which reveals an unsuspected link between heart and adipose tissue. NPs exert potent lipolytic effects (eg, stimulation of hydrolysis of triacylglycerols stored in adipocytes) in isolated human fat cells. 3 When administered intravenously, they potently increase plasma glycerol and nonesterified fatty acid (NEFA) levels; in other words they stimulate lipid mobilization. 4 Before the discovery of the NP pathway, catecholamines and insulin were considered to be the major acute regulators of lipid mobilization in humans: they both act through a cAMP-dependent regulation of lipolysis. In contrast, NPs activate a 3Ј, 5Ј-cyclic guanosine monophosphate (cGMP)-dependent pathway that is completely independent from the cAMP-dependent pathway. 5 The NPs may represent a promising new pathway contributing to the control of lipid mobilization in humans in physiological and pathological conditions. The introductory section

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Section: Natriuretic Peptide Receptorsmentioning

confidence: 99%

An Unsuspected Metabolic Role for Atrial Natriuretic Peptides

Lafontan

Moro

Sengenès

et al. 2005

ATVB

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“…5,6 Recent pharmacologic studies suggested that soluble GC are involved in a chronic model of glomerulonephritis 7,8 ; however, little is known about the role of receptor GC in renal diseases.…”

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confidence: 99%

“…In mammals, seven isoforms of receptor GC have been identified: GC-A through GC-G. 5,6 GC-A and GC-B function as receptors for atrial natriuretic peptide (ANP) and B-type natriuretic peptide, and GC-C mediates the effects of guanylin and uroguanylin on intestinal electrolyte and water transport. 5,6 Endogenous ligands for GC-D, -E, -F, or -G have yet to be identified; therefore, these receptors remain as orphans.…”

mentioning

confidence: 99%

“…5,6 Endogenous ligands for GC-D, -E, -F, or -G have yet to be identified; therefore, these receptors remain as orphans. Despite being an orphan receptor, GC-E has been clearly shown by gene targeting to have a role in maintaining normal retinal structure and function 9 ; the study led to the discovery of numerous mutations in the GC-E gene responsible for several forms of retinal disorders in humans.…”

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confidence: 99%

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Disruption of Guanylyl Cyclase-G Protects against Acute Renal Injury

Lin

Cheng²,

Hou

et al. 2008

Journal of the American Society of Nephrology

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The membrane forms of guanylyl cyclase (GC) serve as cell-surface receptors that synthesize the second messenger cGMP, which mediates diverse cellular processes. Rat kidney contains mRNA for the GC-G isoform, but the role of this receptor in health and disease has not been characterized. It was found that mouse kidney also contains GC-G mRNA, and immunohistochemistry identified GC-G protein in the epithelial cells of the proximal tubule and collecting ducts. Six hours after ischemia-reperfusion (I/R) injury, GC-G mRNA and protein expression increased three-fold and remained upregulated at 24 h. For determination of whether GC-G mediates I/R injury, a mutant mouse with a targeted disruption of the GC-G gene (Gucy2g) was created. At baseline, no histologic abnormalities were observed in GC-G Ϫ/Ϫ mice. After I/R injury, elevations in serum creatinine and urea were attenuated in GC-G Ϫ/Ϫ mice compared with wild-type controls, and this correlated with less tubular disruption, less tubular cell apoptosis, and less caspase-3 activation. Measures of inflammation (number of infiltrating neutrophils, myeloperoxidase activity, and induction of IL-6 and P-selectin) and activation of NF-B were lower in GC-G Ϫ/Ϫ mice compared with wild-type mice. Direct transfer of a GC-G expression plasmid to the kidneys of GC-G Ϫ/Ϫ mice resulted in a dramatically higher mortality after renal I/R injury, further supporting a role for GC-G in mediating injury. In summary, GC-G may act as an early signaling molecule that promotes apoptotic and inflammatory responses in I/R-induced acute renal injury.

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“…L'activation des MAP-kinases est associée à une augmentation des taux intracellulaires d'AMPc et à une phosphorylation de la sérine (Ser 600 ) de la LHS [8,9]. [11]. Dans un premier temps, nous avons découvert que ces peptides exerçaient une action spéci-fique sur la lipolyse in vitro, puis nous avons mis en évi-dence un effet sur la mobilisation des lipides in vivo.…”

Section: Les Voies Classiques De Régulation De La Lipolyse Chez L'hommeunclassified