Guanylyl cyclases: A family of receptor‐linked enzymes

Fülle, Hans-Jürgen; Garbers, David L.

doi:10.1002/cbf.290120303

Cited by 19 publications

(15 citation statements)

References 70 publications

(14 reference statements)

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“…Collectively, these findings suggest that cGMP/NO systems play a beneficial counter‐regulatory role during pneumoperitoneum‐induced renal dysfunction. These observations are in agreement with the vasodilatory and natriuretic properties of cGMP, a second messenger of NPs and NO . cGMP is degraded by PDE5,, which is abundant in the kidney and lungs .…”

Section: Discussionsupporting

confidence: 87%

Phosphodiesterase 5 inhibition protects against increased intra‐abdominal pressure‐induced renal dysfunction in experimental congestive heart failure

Bishara

Abu-Saleh

Awad

et al. 2012

European J of Heart Fail

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AimsCongestive heart failure (CHF) is associated with impaired renal function. Previously, we have demonstrated that rats with decompensated CHF exhibited exaggerated sensitivity to the adverse renal effects of increased increased intraabdominal pressure (IAP) as compared with normal controls. This study tested whether phosphodiesterase 5 (PDE5) inhibition protects against the adverse renal effects of increased IAP in rats with CHF. Methods and resultsFollowing baseline periods, rats with compensated and decompensated CHF induced by the placement of an aorto-caval fistula (ACF), rats with myocardial infarction (MI) induced by left anterior descending (LAD) artery ligation, and sham controls were subjected to consecutive IAPs: 7, 10, or 14 mmHg. Urine flow (V), Na + excretion (U Na V), glomerular filtration rate (GFR), and renal plasma flow (RPF) were determined. The effects of pre-treatment with tadalafil on the adverse renal effects of IAP were examined in rats with decompensated CHF and MI. Elevation of IAP to 10 and 14 mmHg produced linear reductions in these parameters. Basal renal function and haemodynamics were lower in CHF rats. Decompensated CHF rats and MI rats that were subjected to 10 and 14 mmHg exhibited exaggerated declines in V, U Na V, GFR, and RPF. In contrast, no adverse renal effects were observed in rats with compensated CHF subjected to IAP. Pre-treatment of decompensated CHF rats and MI rats with tadalafil ameliorated the adverse renal effects of high IAP. ConclusionDecompensated CHF and MI rats are vulnerable to the adverse renal effects of IAP. Tadalafil abolishes IAP-induced renal dysfunction, supporting a therapeutic role for PDE5 inhibition in CHF associated with ascites.--

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Section: Discussionsupporting

confidence: 87%

Phosphodiesterase 5 inhibition protects against increased intra‐abdominal pressure‐induced renal dysfunction in experimental congestive heart failure

Bishara

Abu-Saleh

Awad

et al. 2012

European J of Heart Fail

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“…cGMP is formed from the catalytic conversion of GTP, by either the cytosolic sGC (the receptor for nitric oxide, NO • ), or by the membrane-bound particulate GC isoform (pGC, activated by the natriuretic peptides ANP and BNP) [7]. Our work and others have indicated that cGMP is a powerful antihypertrophic mediator in the heart [8], [9].…”

Section: Introductionmentioning

confidence: 64%

The Soluble Guanylyl Cyclase Activator Bay 58-2667 Selectively Limits Cardiomyocyte Hypertrophy

et al. 2012

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BackgroundAlthough evidence now suggests cGMP is a negative regulator of cardiac hypertrophy, the direct consequences of the soluble guanylyl cyclase (sGC) activator BAY 58-2667 on cardiac remodeling, independent of changes in hemodynamic load, has not been investigated. In the present study, we tested the hypothesis that the NO•-independent sGC activator BAY 58-2667 inhibits cardiomyocyte hypertrophy in vitro. Concomitant impact of BAY 58-2667 on cardiac fibroblast proliferation, and insights into potential mechanisms of action, were also sought. Results were compared to the sGC stimulator BAY 41-2272.MethodsNeonatal rat cardiomyocytes were incubated with endothelin-1 (ET1, 60nmol/L) in the presence and absence of BAY 41-2272 and BAY 58-2667 (0.01–0.3 µmol/L). Hypertrophic responses and its triggers, as well as cGMP signaling, were determined. The impact of both sGC ligands on basal and stimulated cardiac fibroblast proliferation in vitro was also determined.ResultsWe now demonstrate that BAY 58-2667 (0.01–0.3 µmol/L) elicited concentration-dependent antihypertrophic actions, inhibiting ET1-mediated increases in cardiomyocyte 2D area and de novo protein synthesis, as well as suppressing ET1-induced cardiomyocyte superoxide generation. This was accompanied by potent increases in cardiomyocyte cGMP accumulation and activity of its downstream signal, vasodilator-stimulated phosphoprotein (VASP), without elevating cardiomyocyte cAMP. In contrast, submicromolar concentrations of BAY 58-2667 had no effect on basal or stimulated cardiac fibroblast proliferation. Indeed, only at concentrations ≥10 µmol/L was inhibition of cardiac fibrosis seen in vitro. The effects of BAY 58-2667 in both cell types were mimicked by BAY 41-2272.ConclusionsOur results demonstrate that BAY 58-2667 elicits protective, cardiomyocyte-selective effects in vitro. These actions are associated with sGC activation and are evident in the absence of confounding hemodynamic factors, at low (submicromolar) concentrations. Thus this distinctive sGC ligand may potentially represent an alternative therapeutic approach for limiting myocardial hypertrophy.

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“…GC-D is homologous to other transmembrane guanylyl cyclase receptors where stimulation of the extracellular domain by a peptide leads to activation of the intracellular catalytic domain and production of cGMP (9), suggesting that a cGMP pathway may also be involved in olfactory signaling. The distribution pattern of GC-D mRNA throughout the neuronal layer is similar to the zonal pattern observed for the G-protein coupled odorant receptors (10,11).…”

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confidence: 99%

A subset of olfactory neurons that selectively express cGMP-stimulated phosphodiesterase (PDE2) and guanylyl cyclase-D define a unique olfactory signal transduction pathway

Juilfs

Fülle

Zhao

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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289

317

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Odorant information is encoded by a series of intracellular signal transduction events thought to be mediated primarily by the second messenger cAMP. We have found a subset of olfactory neurons that express the cGMPstimulated phosphodiesterase (PDE2) and guanylyl cyclase-D (GC-D), suggesting that cGMP in these neurons also can have an important regulatory function in olfactory signaling. PDE2 and GC-D are both expressed in olfactory cilia where odorant signaling is initiated; however, only PDE2 is expressed in axons. In contrast to most other olfactory neurons, these neurons appear to project to a distinct group of glomeruli in the olfactory bulb that are similar to the subset that have been termed ''necklace glomeruli.'' Furthermore, this subset of neurons are unique in that they do not contain several of the previously identified components of olfactory signal transduction cascades involving cAMP and calcium, including a calcium͞calmodulin-dependent PDE (PDE1C2), adenylyl cyclase III, and cAMP-specific PDE (PDE4A). Interestingly, these latter three proteins are expressed in the same neurons; however, their subcellular distribution is distinct. PDE1C2 and adenylyl cyclase III are expressed almost exclusively in the olfactory cilia whereas PDE4A is present only in the cell bodies and axons. These data strongly suggest that selective compartmentalization of different PDEs and cyclases is an important feature for the regulation of signal transduction in olfactory neurons and likely in other neurons as well. In addition, the data implies that an olfactory signal transduction pathway specifically modulated by cGMP is present in some neurons of the olfactory neuroepithelium.

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Guanylyl cyclases: A family of receptor‐linked enzymes

Cited by 19 publications

References 70 publications

Phosphodiesterase 5 inhibition protects against increased intra‐abdominal pressure‐induced renal dysfunction in experimental congestive heart failure

Phosphodiesterase 5 inhibition protects against increased intra‐abdominal pressure‐induced renal dysfunction in experimental congestive heart failure

The Soluble Guanylyl Cyclase Activator Bay 58-2667 Selectively Limits Cardiomyocyte Hypertrophy

A subset of olfactory neurons that selectively express cGMP-stimulated phosphodiesterase (PDE2) and guanylyl cyclase-D define a unique olfactory signal transduction pathway

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