Enhanced endothelium-dependent relaxation of rat pulmonary artery following β-adrenergic overstimulation: Involvement of the NO/cGMP/VASP pathway

Davel, Ana Paula; Victório, Jamaira A.; Delbin, Maria Andréia; Fukuda, Lívia Emy; Rossoni, Luciana Venturini

doi:10.1016/j.lfs.2015.01.018

Cited by 19 publications

(16 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…indicating that changes at the post-receptor level must contribute to desensitisation. Such changes at the level of G protein expression (Chambers et al, 1994;, cAMP formation in the presence of direct G protein stimulators (Scarpace et al, 1999), and AC activity Okeke et al, 2017) have been reported, but examples also exist where desensitisation was not accompanied by changes at these levels (Davel et al, 2015;Hutchinson et al, 2000;Scarpace et al, 1999).…”

Section: Evidence Of Synthesis and Conclusionmentioning

confidence: 97%

“…However, the same investigators observed no change in forskolin‐stimulated relaxation in rat urinary bladder after 6 hr of agonist treatment (Michel, ); similarly, rat ileum relaxation induced by forskolin was also found to be unaltered after 4 hr of agonist treatment (Hutchinson et al, ). A study in pulmonary artery demonstrated that a 7 day pretreatment of rats with isoprenaline reduced PDE5 expression (Davel et al, ). While this may be relevant to enhanced endothelial NOS activity in the same study, it is unlikely to have contributed to β‐adrenoceptor function because PDE5 is selective for cGMP, not cAMP; accordingly, relaxation responses to agonists including the β 3 ‐adrenoceptor selective mirabegron were unchanged.…”

Section: β3‐adrenoceptor‐induced Desensitisation Of Camp Signallingmentioning

confidence: 99%

“…Had they normalised to GAPDH expression, as many authors do, the down-regulation of G s and G i1 would have been masked, and the lack of significant regulation of G i3 would have turned into an apparent up-regulation. A study with in vivo pretreatment of rats with isoprenaline for 7 days reported a lack of change of expression of G i1/2 and G i3 protein in pulmonary artery, when normalised for α-actin expression (Davel et al, 2015).…”

Section: Changes In G Proteins Ac and Pdesmentioning

confidence: 99%

“…Relaxation of rat isolated pulmonary artery was assessed after pretreatment with vehicle or 0.3-mg·kg −1 ·day −1 isoprenaline for 7 days (Davel et al, 2015). As an internal control of the action of isoprenaline, the treatment induced right and left ventricular hypertrophy.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Agonist‐induced desensitisation of β₃‐adrenoceptors: Where, when, and how?

Okeke

Angers

Bouvier

et al. 2019

British J Pharmacology

View full text Add to dashboard Cite

β3‐Adrenoceptor agonists have proven useful in the treatment of overactive bladder syndrome, but it is not known whether their efficacy during chronic administration may be limited by receptor‐induced desensitisation. Whereas the β2‐adrenoceptor has phosphorylation sites that are important for desensitisation, the β3‐adrenoceptor lacks these; therefore, it had been assumed that β3‐adrenoceptors are largely resistant to agonist‐induced desensitisation. While all direct comparative studies demonstrate that β3‐adrenoceptors are less susceptible to desensitisation than β2‐adrenoceptors, desensitisation of β3‐adrenoceptors has been observed in many models and treatment settings. Chimeric β2‐ and β3‐adrenoceptors have demonstrated that the C‐terminal tail of the receptor plays an important role in the relative resistance to desensitisation but is not the only relevant factor. While the evidence from some models, such as transfected CHO cells, is inconsistent, it appears that desensitisation is observed more often after long‐term (hours to days) than short‐term (minutes to hours) agonist exposure. When it occurs, desensitisation of β3‐adrenoceptors can involve multiple levels including down‐regulation of its mRNA and the receptor protein and alterations in post‐receptor signalling events. The relative contributions of these mechanistic factors apparently depend on the cell type under investigation. Which if any of these factors is applicable to the human urinary bladder remains to be determined. Linked Articles This article is part of a themed section on Adrenoceptors—New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc

show abstract

Section: Evidence Of Synthesis and Conclusionmentioning

confidence: 97%

Section: β3‐adrenoceptor‐induced Desensitisation Of Camp Signallingmentioning

confidence: 99%

Section: Changes In G Proteins Ac and Pdesmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Agonist‐induced desensitisation of β₃‐adrenoceptors: Where, when, and how?

Okeke

Angers

Bouvier

et al. 2019

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Once activated, PKG causes vascular relaxation via phosphorylation of vasodilator-stimulated phosphoprotein (VASP) in VSMC [16, 21-23]. …”

Section: Introductionmentioning

confidence: 99%

Triiodothyronine Potentiates Vasorelaxation via PKG/VASP Signaling in Vascular Smooth Muscle Cells

Samuel

Zhang

Tang

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Vascular relaxation caused by Triiodothyronine (T3) involves direct activation of endothelial cells (EC) and vascular smooth muscle cells (VSMC). Activation of protein kinase G (PKG) has risen as a novel contributor to the vasorelaxation mechanism triggered by numerous stimuli. We hypothesize that T3-induced vasorelaxation involves PKG/vasodilator-stimulated phosphoprotein (VASP) signaling pathway in VSMC. Methods: Human aortic endothelial cells (HAEC) and VSMC were treated with T3 for short (2 to 60 minutes) and long term (24 hours). Nitric oxide (NO) production was measured using DAF-FM. Expression of protein targets was determined using western blot. For functional studies, rat aortas were isolated and treated with T3 for 20 minutes and mounted in a wire myograph. Relaxation was measured by a concentration-dependent response to acetylcholine (ACh) and sodium nitroprusside (SNP). Results: Aortas stimulated with T3 exhibited augmented sensitivity to ACh and SNP-induced relaxation, endothelium-dependent and endothelium-independent responses, respectively. T3 directly increased vasorelaxation, which was abolished in the presence of a PKG inhibitor. T3 markedly induced phosphorylation of Akt, eNOS and consequently increased NO production in EC. Likewise, T3 induced phosphorylation of VASP at serine 239 via the PKG pathway in VSMC. Conclusion: Our findings have uncovered a PKG/VASP signaling pathway in VSMC as a key molecular mechanism underlying T3-induced vascular relaxation.

show abstract

Nitration of protein kinase G-Iα modulates cyclic nucleotide crosstalk via phosphodiesterase 3A: Implications for acute lung injury

Zemskov

Aggarwal

et al. 2021

Journal of Biological Chemistry

View full text Add to dashboard Cite

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

Enhanced endothelium-dependent relaxation of rat pulmonary artery following β-adrenergic overstimulation: Involvement of the NO/cGMP/VASP pathway

Cited by 19 publications

References 50 publications

Agonist‐induced desensitisation of β₃‐adrenoceptors: Where, when, and how?

Agonist‐induced desensitisation of β₃‐adrenoceptors: Where, when, and how?

Triiodothyronine Potentiates Vasorelaxation via PKG/VASP Signaling in Vascular Smooth Muscle Cells

Nitration of protein kinase G-Iα modulates cyclic nucleotide crosstalk via phosphodiesterase 3A: Implications for acute lung injury

Contact Info

Product

Resources

About

Enhanced endothelium-dependent relaxation of rat pulmonary artery following β-adrenergic overstimulation: Involvement of the NO/cGMP/VASP pathway

Cited by 19 publications

References 50 publications

Agonist‐induced desensitisation of β3‐adrenoceptors: Where, when, and how?

Agonist‐induced desensitisation of β3‐adrenoceptors: Where, when, and how?

Triiodothyronine Potentiates Vasorelaxation via PKG/VASP Signaling in Vascular Smooth Muscle Cells

Nitration of protein kinase G-Iα modulates cyclic nucleotide crosstalk via phosphodiesterase 3A: Implications for acute lung injury

Contact Info

Product

Resources

About

Agonist‐induced desensitisation of β₃‐adrenoceptors: Where, when, and how?

Agonist‐induced desensitisation of β₃‐adrenoceptors: Where, when, and how?