Cyclic GMP transporters

Sager, Georg

doi:10.1016/j.neuint.2004.03.017

Cited by 98 publications

(93 citation statements)

References 97 publications

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“…Intracellular cGMP accumulation is a balance of three major processes: cGMP synthesis by guanylyl cyclases (9,10), cGMP degradation by phosphodiesterases (11), and cGMP extrusion into the medium (12). Thus, suppression of cGMP accumulation by BPIPP can be due to inhibition of guanylyl cyclase activation or to stimulation of cGMP degradation or extrusion.…”

Section: Resultsmentioning

confidence: 99%

Pyridopyrimidine derivatives as inhibitors of cyclic nucleotide synthesis: Application for treatment of diarrhea

Kots¹,

Choi²,

Estrella-Jimenez

et al. 2008

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

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Section: Resultsmentioning

confidence: 99%

Pyridopyrimidine derivatives as inhibitors of cyclic nucleotide synthesis: Application for treatment of diarrhea

Kots¹,

Choi²,

Estrella-Jimenez

et al. 2008

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

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“…It has been demonstrated that cGMP produced within human erythrocytes can be eliminated by phosphodiesterases [59] or by active efflux transporters [60]. Wu et al [32] found that different blood donors express different amounts of both MRP4 and MRP5 on their RBCs.…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide synthetic pathway and cGMP levels are altered in red blood cells from end-stage renal disease patients

et al. 2016

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Red blood cells (RBCs) enzymatically produce nitric oxide (NO) by a functional RBC-nitric oxide synthase (RBC-NOS). NO is a vascular key regulatory molecule. In RBCs its generation is complex and influenced by several factors, including insulin, acetylcholine, and calcium. NO availability is reduced in end-stage renal disease (ESRD) and associated with endothelial dysfunction. We previously demonstrated that, through increased phosphatidylserine membrane exposure, ESRD-RBCs augmented their adhesion to human cultured endothelium, in which NO bioavailability decreased. Since RBC-NOS-dependent NO production in ESRD is unknown, this study aimed to investigate RBC-NOS levels/activation, NO production/bioavailability in RBCs from healthy control subjects (C, N = 18) and ESRD patients (N = 27). Although RBC-NOS expression was lower in ESRDRBCs, NO, cyclic guanosine monophosphate (cGMP), RBC-NOS Serine1177 phosphorylation level and eNOS/ Calmodulin (CaM)/Heat Shock Protein-90 (HSP90) interaction levels were higher in ESRD-RBCs, indicating increased enzyme activation. Conversely, following RBCs stimulation with insulin or ionomycin, NO and cGMP levels were significantly lower in ESRD-than in C-RBCs, suggesting that uremia might reduce the RBC-NOS response to further stimuli. Additionally, the activity of multidrug-resistance-associated protein-4 (MRP4; cGMPmembrane transporter) was significantly lower in ESRDRBCs, suggesting a possible compromised efflux of cGMP across the ESRD-RBCs membrane. This study for the first time showed highest basal RBC-NOS activation in ESRDRBCs, possibly to reduce the negative impact of decreased NOS expression. It is further conceivable that high NO production only partially affects cell function of ESRDRBCs maybe because in vivo they are unable to respond to physiologic stimuli, such as calcium and/or insulin.Keywords End-stage renal disease Á Red blood cells Á Nitric oxide Á cGMP Á Nitric oxide synthase Mario Bonomini, and Assunta Pandolfi have contributed equally to the study.Electronic supplementary material The online version of this article

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“…Other candidates for paracrine signaling are ATP and cGMP (28,29), but several aspects argue against a relevance for these nucleotides in the fight-or-flight response: first, release of ATP from CMs is reported to occur under stress conditions, such as hypoxia or mechanical stretch (28), but not during normal contraction (30). Under our experimental conditions, i.e., in the presence of Iso, we did not observe increased export of ATP or cGMP (Supplemental Figure 7).…”

Section: Methodsmentioning

confidence: 99%

Cardiac myocyte–secreted cAMP exerts paracrine action via adenosine receptor activation

Sassi¹,

Ahles²,

Truong³

et al. 2014

J. Clin. Invest.

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International audienceAcute stimulation of cardiac β-adrenoceptors is crucial to increasing cardiac function under stress; however, sustained β-adrenergic stimulation has been implicated in pathological myocardial remodeling and heart failure. Here, we have demonstrated that export of cAMP from cardiac myocytes is an intrinsic cardioprotective mechanism in response to cardiac stress. We report that infusion of cAMP into mice averted myocardial hypertrophy and fibrosis in a disease model of cardiac pressure overload. The protective effect of exogenous cAMP required adenosine receptor signaling. This observation led to the identification of a potent paracrine mechanism that is dependent on secreted cAMP. Specifically, FRET-based imaging of cAMP formation in primary cells and in myocardial tissue from murine hearts revealed that cardiomyocytes depend on the transporter ABCC4 to export cAMP as an extracellular signal. Extracellular cAMP, through its metabolite adenosine, reduced cardiomyocyte cAMP formation and hypertrophy by activating A1 adenosine receptors while delivering an antifibrotic signal to cardiac fibroblasts by A2 adenosine receptor activation. Together, our data reveal a paracrine role for secreted cAMP in intercellular signaling in the myocardium, and we postulate that secreted cAMP may also constitute an important signal in other tissues

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Cyclic GMP transporters

Cited by 98 publications

References 97 publications

Pyridopyrimidine derivatives as inhibitors of cyclic nucleotide synthesis: Application for treatment of diarrhea

Pyridopyrimidine derivatives as inhibitors of cyclic nucleotide synthesis: Application for treatment of diarrhea

Nitric oxide synthetic pathway and cGMP levels are altered in red blood cells from end-stage renal disease patients

Cardiac myocyte–secreted cAMP exerts paracrine action via adenosine receptor activation

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