Novel guanylyl cyclase inhibitor, ODQ reveals role of nitric oxide, but not of cyclic GMP in endothelin‐1 secretion

Brünner, Friedrich; Stessel, Heike; Kukovetz, W. R.

doi:10.1016/0014-5793(95)01297-x

Cited by 74 publications

(49 citation statements)

References 25 publications

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“…ODQ (10 M), a specific inhibitor of sGC activation (40)(41)(42), prevented the PROLI-NO (50 nM) induced increase of cGMP (Fig. 4E), indicating that the observed rise in [cGMP] i is indeed due to NO-induced activation of sGC.…”

Section: Kinetic Spectral Analysis and Environmental Stability Of ␦-mentioning

confidence: 90%

Differential patterning of cGMP in vascular smooth muscle cells revealed by single GFP-linked biosensors

Nausch

Ledoux

Bonev

et al. 2008

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

151

174

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Section: Kinetic Spectral Analysis and Environmental Stability Of ␦-mentioning

confidence: 90%

Differential patterning of cGMP in vascular smooth muscle cells revealed by single GFP-linked biosensors

Nausch

Ledoux

Bonev

et al. 2008

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

151

174

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“…(3) The expression level of sGC concomitantly decreased with the reduction of NOS expression when larvae were approaching attachment and metamorphosis. As sGC is the most prominent downstream effector of NO signaling, the selective sGC inhibitor ODQ has been widely used as a tool to study the interaction among NO, GC and cGMP (Brunner et al, 1995). Recently, using ODQ, different researchers have suggested the involvement of cGMP in larval metamorphosis of several marine invertebrates (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…) of the specific GC inhibitor ODQ was used to treat the cyprids (Brunner et al, 1995). To determine whether the biological function of NO during larval settlement is through the second messenger cGMP, the cyprid larvae were coincubated with a dilution series (2.5, 5, 10 and 20mmoll -1 ) of ODQ and 1000mmoll -1 SNP.…”

Section: Modulation Of the Endogenous Cgmp Levelmentioning

confidence: 99%

“…Generally, the up-regulation of NO will lead to the activation of GC, which subsequently promotes the formation of cGMP (Lucas et al, 2000). To evaluate whether cGMP is involved in regulating B. amphitrite larval settlement, cyprids were incubated with a potent and specific sGC inhibitor, ODQ (Brunner et al, 1995). If the inhibitive effect of NO in larval settlement is via the elevation of cGMP, suppression of cGMP-producing enzyme (sGC) activity should initiate larval settlement.…”

Section: Cgmp Is Involved In Larval Settlementmentioning

confidence: 99%

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The regulatory role of the NO/cGMP signal transduction cascade during larval attachment and metamorphosis of the barnacleBalanus (=Amphibalanus) amphitrite

Zhang

et al. 2012

Journal of Experimental Biology

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SUMMARYThe barnacle Balanus amphitrite is among the most dominant fouling species on intertidal rocky shores in tropical and subtropical areas and is thus a target organism in antifouling research. After being released from adults, the swimming nauplius undertakes six molting cycles and then transforms into a cyprid. Using paired antennules, a competent cyprid actively explores and selects a suitable substratum for attachment and metamorphosis (collectively known as settlement). This selection process involves the reception of exogenous signals and subsequent endogenous signal transduction. To investigate the involvement of nitric oxide (NO) and cyclic GMP (cGMP) during larval settlement of B. amphitrite, we examined the effects of an NO donor and an NO scavenger, two nitric oxide synthase (NOS) inhibitors and a soluble guanylyl cyclase (sGC) inhibitor on settling cyprids. We found that the NO donor sodium nitroprusside (SNP) inhibited larval settlement in a dose-dependent manner. In contrast, both the NO scavenger carboxy-PTIO and the NOS inhibitors aminoguanidine hemisulfate (AGH) and S-methylisothiourea sulfate (SMIS) significantly accelerated larval settlement. Suppression of the downstream guanylyl cyclase (GC) activity using a GC-selective inhibitor ODQ could also significantly accelerate larval settlement. Interestingly, the settlement inhibition effects of SNP could be attenuated by ODQ at all concentrations tested. In the developmental expression profiling of NOS and sGC, the lowest expression of both genes was detected in the cyprid stage, a crucial stage for the larval decision to attach and metamorphose. In summary, we concluded that NO regulates larval settlement via mediating downstream cGMP signaling. Supplementary material available online at

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“…This dual-application protocol was used in the following experiments to normalize the changes in [Ca 2ϩ ] mt caused by Sper/NO (or other interventions) in individual cells. We used the NO donor Sper/NO in the range of 50 -500 M, which produces NO levels of 0.5-3 M as estimated by us and reported by others (10,13,47). Therefore, the low concentrations of Sper/NO (50 -100 M) imitate NO production observed under physiological conditions (ϳ0.5-1 M NO), whereas higher concentrations of Sper/NO (Ͼ100 M) produce NO in the range typical for pathological conditions (Ͼ1 M NO) (24).…”

Section: Effect Of No On Mitochondrial Ca 2ϩ Uptakementioning

confidence: 99%

Modulation of mitochondrial Ca²⁺ by nitric oxide in cultured bovine vascular endothelial cells

Dedkova

Blatter

2005

American Journal of Physiology-Cell Physiology

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-In the present study, we used laser scanning confocal microscopy in combination with fluorescent indicator dyes to investigate the effects of nitric oxide (NO) produced endogenously by stimulation of the mitochondria-specific NO synthase (mtNOS) or applied exogenously through a NO donor, on mitochondrial Ca 2ϩ uptake, membrane potential, and gating of mitochondrial permeability transition pore (PTP) in permeabilized cultured calf pulmonary artery endothelial (CPAE) cells. Higher concentrations (100 -500 M) of the NO donor spermine NONOate (Sper/NO) significantly reduced mitochondrial Ca 2ϩ uptake and Ca 2ϩ extrusion rates, whereas low concentrations of Sper/NO (Ͻ100 M) had no effect on mitochondrial Ca 2ϩ levels ([Ca 2ϩ ]mt). Stimulation of mitochondrial NO production by incubating cells with 1 mM L-arginine also decreased mitochondrial Ca 2ϩ uptake, whereas inhibition of mtNOS with 10 M L-N 5 -(1-iminoethyl)ornithine resulted in a significant increase of [Ca 2ϩ ]mt. Sper/NO application caused a dose-dependent sustained mitochondrial depolarization as revealed with the voltage-sensitive dye tetramethylrhodamine ethyl ester (TMRE). Blocking mtNOS hyperpolarized basal mitochondrial membrane potential and partially prevented Ca 2ϩ -induced decrease in TMRE fluorescence. Higher concentrations of Sper/NO (100 -500 M) induced PTP opening, whereas lower concentrations (Ͻ100 M) had no effect. The data demonstrate that in calf pulmonary artery endothelial cells, stimulation of mitochondrial Ca 2ϩ uptake can activate NO production in mitochondria that in turn can modulate mitochondrial Ca 2ϩ uptake and efflux, demonstrating a negative feedback regulation. This mechanism may be particularly important to protect against mitochondrial Ca 2ϩ overload under pathological conditions where cellular [NO] can reach very high levels. nitric oxide synthase; permeability transition pore; endothelium IN THE VASCULAR ENDOTHELIUM, nitric oxide (NO) plays an important regulatory role. NO, which is synthesized in a Ca 2ϩ -dependent manner by the endothelial NO synthase (eNOS), acts on vascular smooth muscle cells in the vessel wall as an endothelium-derived relaxing factor (40). We have demonstrated previously (19) that in vascular endothelial cells NO synthesis is not only Ca 2ϩ dependent but also under an autoregulatory control that involves NO-dependent regulation of cytoplasmic Ca 2ϩ . Considering the known inhibitory effects of NO on cell respiration (6,7,18) and the recent discovery of a mitochondrial NOS (mtNOS) in endothelial cells (20), the question arises whether a similar autoregulatory function of NO in endothelial cells also affects mitochondrial Ca 2ϩ uptake.Although mtNOS has been discovered in a variety of cell types (3,4,20,21,25,26,35,36,38,49,52), the functional implications of NO produced locally by mitochondria for mitochondrial energy metabolism and Ca 2ϩ homeostasis are much less explored and not well understood. NO is known to be a mediator of Ca 2ϩ homeostasis in a highly complex and cell-specific manner (17)...

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Novel guanylyl cyclase inhibitor, ODQ reveals role of nitric oxide, but not of cyclic GMP in endothelin‐1 secretion

Cited by 74 publications

References 25 publications

Differential patterning of cGMP in vascular smooth muscle cells revealed by single GFP-linked biosensors

Differential patterning of cGMP in vascular smooth muscle cells revealed by single GFP-linked biosensors

The regulatory role of the NO/cGMP signal transduction cascade during larval attachment and metamorphosis of the barnacleBalanus (=Amphibalanus) amphitrite

Modulation of mitochondrial Ca²⁺ by nitric oxide in cultured bovine vascular endothelial cells

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Novel guanylyl cyclase inhibitor, ODQ reveals role of nitric oxide, but not of cyclic GMP in endothelin‐1 secretion

Cited by 74 publications

References 25 publications

Differential patterning of cGMP in vascular smooth muscle cells revealed by single GFP-linked biosensors

Differential patterning of cGMP in vascular smooth muscle cells revealed by single GFP-linked biosensors

The regulatory role of the NO/cGMP signal transduction cascade during larval attachment and metamorphosis of the barnacleBalanus (=Amphibalanus) amphitrite

Modulation of mitochondrial Ca2+ by nitric oxide in cultured bovine vascular endothelial cells

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Modulation of mitochondrial Ca²⁺ by nitric oxide in cultured bovine vascular endothelial cells