Quantification of cyclic AMP and cyclic GMP levels in Krebs-Henseleit solution by LC-MS/MS: Application in washed platelet aggregation samples

Nash, Charles Elliot Serpellone; Antunes, Natalícia J.; Silva, Weverton Castro Coelho; Campos, Rafael; Nucci, Gilberto De

doi:10.1016/j.jchromb.2022.123472

Cited by 8 publications

(4 citation statements)

References 29 publications

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“…However, it is unlikely that 6-ND acts as a PDE3 inhibitor since, when incubated in the rat isolated right atrium, it abolishes the concentration-dependent increase in the atrial rate induced by milrinone or cilostazol [59]. In addition, incubation of 6-ND with human washed platelets was not accompanied by a change in nucleotide levels [60].…”

Section: Discussionmentioning

confidence: 97%

6-Nitrodopamine Is the Most Potent Endogenous Positive Inotropic Agent in the Isolated Rat Heart

Britto-Júnior,

Medeiros-Teixeira,

Lima

et al. 2023

Life

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Background: 6-nitrodopamine released from rat isolated atria exerts positive chronotropic action, being more potent than noradrenaline, adrenaline, and dopamine. Here, we determined whether 6-nitrodopamine is released from rat isolated ventricles (RIV) and modulates heart inotropism. Methods: Catecholamines released from RIV were quantified by LC-MS/MS and their effects on heart inotropism were evaluated by measuring left ventricular developed pressure (LVDP) in Langendorff’s preparation. Results: 6-nitrodopamine was the major released catecholamine from RIV. Incubation with L-NAME (100 µM), but not with tetrodotoxin (1 µM), caused a significant reduction in 6-nitrodopamine basal release. 6-nitrodopamine release was significantly reduced in ventricles obtained from L-NAME chronically treated animals. 6-nitrodopamine (0.01 pmol) caused significant increases in LVDP and dP/dtmax, whereas dopamine and noradrenaline required 10 pmol, and adrenaline required 100 pmol, to induce similar increases in LVDP and dP/dtmax. The infusion of atenolol (10 nM) reduced basal LVDP and blocked the increases in LVDP induced by 6-ND (0.01 pmol), without affecting the increases in LVDP induced by 10 nmol of dopamine and noradrenaline and that induced by adrenaline (100 nmol). Conclusions: 6-nitrodopamine is the major catecholamine released from rat isolated ventricles. It is 1000 times more potent than dopamine and noradrenaline and is selectively blocked by atenolol, indicating that 6-ND is a main regulator of heart inotropism.

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Section: Discussionmentioning

confidence: 97%

6-Nitrodopamine Is the Most Potent Endogenous Positive Inotropic Agent in the Isolated Rat Heart

Britto-Júnior,

Medeiros-Teixeira,

Lima

et al. 2023

Life

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“…Since the relaxation of the vascular smooth muscle is attributed to soluble guanylate cyclase and cGMP generation ( 48 ), and the relaxation induced by 6-ND was unaltered by soluble guanylyl cyclase inhibition, the synthesis of 6-ND constitutes an additional pathway by which NO causes vasorelaxation. Indeed, 6-nitrodopamine failed to increase cGMP levels in human washed platelets ( 49 ). The relaxation caused by 6-ND was not affected by pretreatment of the vascular rings with the dopamine D 1 R antagonist SCH-23390 ( 50 ), supporting the hypothesis that 6-ND is acting as a selective D 2 -like antagonist.…”

Section: Actions Of 6-nitrodopamine In the Vascular Smooth Musclementioning

confidence: 99%

Endothelium-Derived Dopamine and 6-Nitrodopamine in the Cardiovascular System

Zatz,

De Nucci

2024

Physiology

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The review deals with the release of endothelium-derived dopamine and 6-nitrodopamine (6-ND) and its effects on isolated vascular tissues and isolated heart. Human isolated umbilical cord vessels, human popliteal vessels, non-human primate vessels, and reptilia aortae, present basal release of both dopamine and 6-ND. The 6-ND basal release was significantly reduced when the tissues were treated with L-NAME and virtually abolished when the endothelium was mechanically removed. 6-Nitrodopamine is a potent vasodilator, and the mechanism of action responsible for this effect is the antagonism on dopamine D2-like receptor. As a vasodilator, 6-ND constitutes a novel mechanism by which NO modulates vascular tone. The basal release of 6-ND was substantially decreased in eNOS-/- mice and not altered in nNOS-/- mice, indicating a non-neurogenic source for 6-ND in the heart. Indeed, in rat isolated right atrium, the release of 6-ND was not affected when the atria were treated with tetrodotoxin. In the rat isolated right atrium, 6-ND is the most potent endogenous positive chronotropic agent, and in Langendorff's heart preparation, it is the most potent endogenous positive inotropic agent. The positive chronotropic and inotropic effects of 6-ND are antagonized by β1-adrenoceptor antagonists at concentrations that do not affect the effects induced by noradrenaline, adrenaline, and dopamine, indicating that blockade of 6-ND receptor is the major modulator of heart chronotropism and inotropism. The review proposes that endothelium-derived catecholamines may constitute a major mechanism for control of vascular tone and heart functions, in contrast to the overrated role attributed to the autonomic nervous system.

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“…LC-MS/MS detection of cAMP and 5-HIAA LC-MS/MS was used to detect cAMP and 5-HIAA concentrations, as previously described [51,52]. Liquid chromatography was performed using a Prominence® HPLC system (Shimadzu, Tokyo, Japan), comprising a solvent delivery unit LC-20AD, an autosampler SIL-20AC, and a column oven CTO-20AC.…”

Section: Rna Extraction Library Construction and Bioinformatics Analy...mentioning

confidence: 99%

Gut microbiota-derived 5-hydroxyindoleacetic acid from Pumpkin Polysaccharides supplementation alleviates colitis through Epac/Rap1 signaling activation

Zhang

Wang

et al. 2023

Preprint

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Aims Polysaccharides from Pumpkin (Cucurbita moschata Duchesne) (PP) have many pharmacological activities, including anti-oxidant, immune, and intestinal microbiota regulation. These activities have provided some reminders of its potential therapeutic effect on ulcerative colitis (UC), but this has not yet been confirmed. This study explores the potential modulatory roles of gut microbial metabolites (5-hydroxyindole acetic acid, 5-HIAA) after PP treatment in protecting against UC and to elucidate the underlying molecular mechanisms. Results The average molecular weight of PP was 3.10 × 105 Da, and PP mainly comprised Mannose, Rhamnose, Galacturonic acid, Galactosamine, Glucose, and Xylose with molar ratios of 1.58:3.51:34.54:1.00:3.25:3.02. PPs (50, 100 mg/kg) could significantly resist dextran sodium sulfate (DSS) induced UC on C57BL/6 mice by improving gut microbiota dysbiosis and intestinal mucosal barrier function. Metabolomic profiling analysis showed that PP supplementation resulted in the enrichment of 5-HIAA, which exhibited individual and synergistic anti-UC activities. The results of the transcriptome and confirmatory experiments suggested that Rap1 pathway activation may participate in the anti-UC effect of PPs. 8-pCPT-2’-O-Me-cAMP (Epac/Rap1 signaling antagonist) showed similar anti-UC activity to PP and 5-HIAA, while the effect of ESI-05 (Epac/Rap1 signaling inhibitor) was opposite. Furthermore, exogenous treatment with 5-HIAA activated the Epac/Rap1 signaling pathway both in vitro and in vivo, which may be related to elevated cAMP levels in the colon. Conclusions This study revealed that PP could be developed to treat UC and other diseases associated with an imbalance in the intestinal microbiota. The gut microbiota-5-HIAA-Epac/Rap1 axis plays an important role in intestinal homeostasis and may provide a novel approach for the prevention of UC by manipulating gut microbial serotonin metabolites.

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Quantification of cyclic AMP and cyclic GMP levels in Krebs-Henseleit solution by LC-MS/MS: Application in washed platelet aggregation samples

Cited by 8 publications

References 29 publications

6-Nitrodopamine Is the Most Potent Endogenous Positive Inotropic Agent in the Isolated Rat Heart

6-Nitrodopamine Is the Most Potent Endogenous Positive Inotropic Agent in the Isolated Rat Heart

Endothelium-Derived Dopamine and 6-Nitrodopamine in the Cardiovascular System

Gut microbiota-derived 5-hydroxyindoleacetic acid from Pumpkin Polysaccharides supplementation alleviates colitis through Epac/Rap1 signaling activation

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