Modulation of Bradykinin Receptor Ligand Binding Affinity and Its Coupled G-proteins by Nitric Oxide

Miyamoto, Atsushi; Laufs, Ulrich; Pardo, Cecilio; Liao, James K.

doi:10.1074/jbc.272.31.19601

Cited by 68 publications

(46 citation statements)

References 36 publications

(44 reference statements)

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“…However, it was within the range reported for cultured airway epithelial cells (29). The number of binding sites/cell (B max ) was approximately equal to that which has been reported for bovine aortic endothelium (24).…”

Section: Discussionsupporting

confidence: 49%

“…Our study of B 2 receptor binding characteristics confirmed the presence of B 2 receptors and demonstrated similar numbers of binding sites and bradykinin binding affinity in the two bronchial endothelial cell types. These receptors demonstrated a somewhat lower binding affinity (K d ϭ 5-6 nM) compared with that reported for bovine systemic and pulmonary endothelium (K d ϭ 0.5-2.0 nM) (24). However, it was within the range reported for cultured airway epithelial cells (29).…”

Section: Discussionmentioning

confidence: 42%

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Heterogeneity of bronchial endothelial cell permeability

Moldobaeva

Wagner

2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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In vivo models of airway inflammation suggest that most protein transudation occurs from bronchial microcirculation. However, due to technical limitations in the isolation and culture of bronchial endothelial cells, most studies of lung vascular permeability have focused on pulmonary endothelium. Thus conditions for culture of sheep bronchial artery endothelial cells (BAEC) and bronchial microvascular endothelial cells (BMVEC) were established. The bronchial artery and the mainstem bronchi, stripped of epithelium, were dissected, and endothelial cells were isolated by enzymatic treatment. BAEC and BMVEC demonstrated positive staining for factor VIII-related antigen, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate-labeled low-density lipoprotein, and PECAM-1. Radioligand binding studies confirmed equivalent numbers of bradykinin B2 receptors on BAEC and BMVEC. Permeability of BAEC and BMVEC was determined after treatment with bradykinin and thrombin by comparing the translocation of FITC-dextran (mol wt 9,500) across confluent monolayers ( n = 10–12). Bradykinin caused a maximal increase in permeability in BAEC (165% increase) and BMVEC (144% increase) by 15 min compared with vehicle controls. Thrombin treatment altered BMVEC permeability only, reaching a maximal response at 60 min (109% increase). These results demonstrate bronchial endothelial cell heterogeneity and establish methods to determine intracellular mechanisms contributing to airway disease in relevant cell systems.

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Section: Discussionsupporting

confidence: 49%

Section: Discussionmentioning

confidence: 42%

Heterogeneity of bronchial endothelial cell permeability

Moldobaeva

Wagner

2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…(2). S-nitrosothiols also decreased coupling of M 2 muscarinic, bradykinin, and AT 1 GPCR to their respective G proteins (5, 7) (22). NO does have other effects on GPCR signaling, including desensitization.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have reported effects of NO on signaling through the ␤ 2 -adrenergic receptors, as well as bradykinin, M 2 muscarinic, thromboxane, and AT 1 GPCRs. (2,5,22,31,32). The effects of NO on these GPCR-mediated responses have both cGMP-dependent and -independent components that, together with our data on the 5-HT GPCR system (23), raise the issue of cGMP-independent regulation of GPCRs by S-nitrosothiols as a general physiological mechanism for the regulation of vascular signal transduction.…”

mentioning

confidence: 88%

S-nitrosoglutathione inhibits α₁-adrenergic receptor-mediated vasoconstriction and ligand binding in pulmonary artery

Nozik‐Grayck¹,

Whalen²,

Stamler³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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-Endogenous nitric oxide donor compounds (S-nitrosothiols) contribute to low vascular tone by both cGMP-dependent and -independent pathways. We have reported that S-nitrosoglutathione (GSNO) inhibits 5-hydroxytryptamine (5-HT)-mediated pulmonary vasoconstriction via a cGMP-independent mechanism likely involving S-nitrosylation of its G proteincoupled receptor (GPCR) system. Because catecholamines, like 5-HT, constrict lung vessels via a GPCR coupled to G q, we hypothesized that S-nitrosothiols modify the ␣ 1-adrenergic GPCR system to inhibit pulmonary vasoconstriction by receptor agonists, e.g., phenylephrine (PE). Rat pulmonary artery rings were pretreated for 30 min with and without an S-nitrosothiol, either GSNO or S-nitrosocysteine (CSNO), and constricted with sequential concentrations of PE (10 Ϫ8 -10 Ϫ6 M). Effective cGMP-dependence was tested in rings pretreated with soluble guanylate cyclase inhibitors {either 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or LY-83583} or G kinase inhibitor (KT-5823), and a thiol reductant [dithiothreitol (DTT)] was used to test reversibility of S-nitrosylation. Both S-nitrosothiols attenuated the PE dose response. The GSNO effect was not prevented by LY-83583, ODQ, or KT-5823, indicating cGMP independence. GSNO inhibition was reversed by DTT, consistent with S-nitrosylation or other GSNOmediated cysteine modifications. In CSNO-treated lung protein, the ␣ 1-adrenergic receptor was shown to undergo S-nitrosylation in vitro using a biotin switch assay. Studies of ␣1-adrenergic receptor subtype expression and receptor density by saturation binding with 125 I-HEAT showed that GSNO decreased ␣1-adrenergic receptor density but did not alter affinity for antagonist or agonist. These data demonstrate a novel cGMP-independent mechanism of reversible ␣1-adrenergic receptor inhibition by S-nitrosothiols. nitric oxide; S-nitrosylation; G protein-coupled receptor; guanosine 3Ј,5Ј-cyclic monophosphate THE LOW-RESISTANCE PULMONARY VASCULAR CIRCUIT is regulated by multiple neural, humoral, and endocrine factors among which the endothelium-derived relaxing factor, nitric oxide (NO), plays a fundamental role. NO bioactivity in the pulmonary circulation is present in the form of NO donor compounds (S-nitrosothiols) that maintain low vascular tone by both cGMP-dependent and -independent pathways (13). NO released from endothelial cells activates guanylate cyclase in vascular smooth muscle cells to increase cGMP levels, which in turn relaxes vascular smooth muscle. NO also exerts cGMPindependent effects on the smooth muscle including (but not limited to) stimulating Na ϩ -K ϩ -ATPase activity, modifying K ϩ and Ca 2ϩ channels, and decreasing the sensitivity to, or release of, vasoconstrictors (1,6,12,17,24).We previously demonstrated that pulmonary vasoconstriction elicited by serotonin (5-hydroxytryptamine, 5-HT) is reversibly inhibited by the NO donor S-nitrosoglutathione (GSNO) (23). In addition, use of nitric oxide synthase (NOS) inhibitors or removal of the endothelium to decrease NO...

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“…27 In addition, in endothelial cells, NO has been shown to selectively inhibit G proteins of the G i and G q family but not those of the G s family, and that this modulation of G proteins could have a permissive action on the G s -AC pathway. 28 Therefore, it is possible that NO can activate AC via the potential modulation of G protein.…”

Section: Involvement Of Cgmp and Campmentioning

confidence: 99%

Nitric Oxide Modulates Cardiac Na ⁺ Channel via Protein Kinase A and Protein Kinase G

Ahmmed

Dong

et al. 2001

Circulation Research

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Abstract-We directly tested the effects of nitric oxide (NO) on Na ϩ channels in guinea pig and mouse ventricular myocytes using patch-clamp recordings. We have previously shown that NO donors have no observed effects on expressed Na ϩ channels. In contrast, NO (half-blocking concentration of 523 nmol/L) significantly reduces peak whole-cell Na ϩ current (I Na ) in isolated ventricular myocytes. The inhibitory effect of NO on I Na was not associated with changes in activation, inactivation, or reactivation kinetics. At the single-channel level, the reduction in macroscopic current was mediated by a decrease in open probability and/or a decrease in the number of functional channels with no change in single-channel conductance. Application of cell permeable analogs of cGMP or cAMP mimics the inhibitory effects of NO. Furthermore, the effects of NO on I Na can only be blocked by inhibition of both cGMP and cAMP pathways. Sulfhydryl-reducing agent does not reverse the effect of NO. In summary, although NO exerts its action via the known guanylyl cyclase (GC)/cGMP pathway, our findings provide evidence that NO can mediate its function via a GC/cGMP-independent mechanism involving the activation of adynylyl cyclase (AC) and cAMP-dependent protein kinase. Key Words: nitric oxide Ⅲ cardiac Na ϩ current Ⅲ protein kinase A Ⅲ protein kinase G N itric oxide (NO) is a uniquely diffusible and reactive molecular messenger, which is found in abundance and plays important regulatory roles in different systems throughout the body. 1 In the cardiovascular system, NO is the major endothelium-derived relaxing factor (EDRF) and causes vasodilation and reduces blood pressure. 2 In addition, NO functions as an important endogenous inhibitor of vascular lesion formation. 3 The coronary endothelium is responsible for the bulk of the endogenous, physiological production of NO. 4 However, NO can also be produced within the cardiac myocytes themselves by the constitutive NO synthase. 5 NO modulates cardiac contractility both in vitro and in vivo. 6 More recently, it was shown that NO can regulate both adenylyl cyclase (AC) and guanylyl cyclase (GC) in cardiac myocytes. High levels of NO induce large increases in cGMP and a negative inotropic effect, whereas low levels of NO increase cAMP and induce a positive contractile response. 7 We have previously shown using heterologous expression systems that although Ca 2ϩ channel can be directly modulated by NO, Na ϩ channels are unaffected by direct NO modulation. 8 Here, we show that NO modulates Na ϩ channels in native cardiac myocytes. In addition, we provide evidence to demonstrate that NO modulates Na ϩ channels via second messenger pathways through activation of protein kinase G (PKG) and protein kinase A (PKA). Materials and MethodsSingle left ventricular myocytes were isolated from guinea pigs and mice (Charles River Laboratories, Wilmington, Mass) as previously described. 9 See further details in the expanded Materials and Methods section that can be found in the online data supplement av...

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Modulation of Bradykinin Receptor Ligand Binding Affinity and Its Coupled G-proteins by Nitric Oxide

Cited by 68 publications

References 36 publications

Heterogeneity of bronchial endothelial cell permeability

Heterogeneity of bronchial endothelial cell permeability

S-nitrosoglutathione inhibits α₁-adrenergic receptor-mediated vasoconstriction and ligand binding in pulmonary artery

Nitric Oxide Modulates Cardiac Na ⁺ Channel via Protein Kinase A and Protein Kinase G

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Modulation of Bradykinin Receptor Ligand Binding Affinity and Its Coupled G-proteins by Nitric Oxide

Cited by 68 publications

References 36 publications

Heterogeneity of bronchial endothelial cell permeability

Heterogeneity of bronchial endothelial cell permeability

S-nitrosoglutathione inhibits α1-adrenergic receptor-mediated vasoconstriction and ligand binding in pulmonary artery

Nitric Oxide Modulates Cardiac Na + Channel via Protein Kinase A and Protein Kinase G

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S-nitrosoglutathione inhibits α₁-adrenergic receptor-mediated vasoconstriction and ligand binding in pulmonary artery

Nitric Oxide Modulates Cardiac Na ⁺ Channel via Protein Kinase A and Protein Kinase G