Cross-talk with β2-adrenoceptors enhances ligand affinity properties from endothelial alpha1D-adrenoceptors that mediates carotid relaxation

Pernomian, Laena; Gomes, Mayara Santos; Restini, Carolina Baraldi Araújo; Pupo, André S.; Oliveira, Ana Maria de

doi:10.1111/jphp.12105

Cited by 16 publications

(13 citation statements)

References 35 publications

(60 reference statements)

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“…This is not without precedent, as at least for the rat carotid artery it was shown previously that functional cross-talk with β-ARs can result in α1D-AR-mediated relaxation [44,45]. Therefore, it will be necessary to further define the receptors involved in redistribution to the subcortex with selective antagonists against various adrenergic receptors in future work.…”

Section: Discussionmentioning

confidence: 99%

Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion in a Sheep Model: Critical Role of α1-Adrenergic Signaling

Schiffner

Bischoff

Rakers

et al. 2017

IJMS

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Background: Maintenance of brain circulation during shock is sufficient to prevent subcortical injury but the cerebral cortex is not spared. This suggests area-specific regulation of cerebral blood flow (CBF) during hemorrhage. Methods: Cortical and subcortical CBF were continuously measured during blood loss (≤50%) and subsequent reperfusion using laser Doppler flowmetry. Blood gases, mean arterial blood pressure (MABP), heart rate and renal blood flow were also monitored. Urapidil was used for α1A-adrenergic receptor blockade in dosages, which did not modify the MABP-response to blood loss. Western blot and quantitative reverse transcription polymerase chain reactions were used to determine adrenergic receptor expression in brain arterioles. Results: During hypovolemia subcortical CBF was maintained at 81 ± 6% of baseline, whereas cortical CBF decreased to 40 ± 4% (p < 0.001). Reperfusion led to peak CBFs of about 70% above baseline in both brain regions. α1A-Adrenergic blockade massively reduced subcortical CBF during hemorrhage and reperfusion, and prevented hyperperfusion during reperfusion in the cortex. α1A-mRNA expression was significantly higher in the cortex, whereas α1D-mRNA expression was higher in the subcortex (p < 0.001). Conclusions: α1-Adrenergic receptors are critical for perfusion redistribution: activity of the α1A-receptor subtype is a prerequisite for redistribution of CBF, whereas the α1D-receptor subtype may determine the magnitude of redistribution responses.

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Section: Discussionmentioning

confidence: 99%

Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion in a Sheep Model: Critical Role of α1-Adrenergic Signaling

Schiffner

Bischoff

Rakers

et al. 2017

IJMS

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“…Systematic coexpression with 28 other class A GPCRs revealed that heteromerization with a 1B -or b 2 -AR is required for the cell surface of a 1D -AR (Hague et al, 2004;Uberti et al, 2005). However, a 1D -AR stimulates the contraction of carotid arteries in a 1B -AR knockout mice (Deighan et al, 2005), suggesting that effective trafficking of a 1D -AR to the cell surface is mediated by, for example, native b 2 -AR (Pernomian et al, 2013).…”

Section: Functional Evidence For Gpcr Dimers In Native Tissuementioning

confidence: 99%

G Protein–Coupled Receptor Multimers: A Question Still Open Despite the Use of Novel Approaches

Vischer

Castro

2015

Mol Pharmacol

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Heteromerization of G protein-coupled receptors (GPCRs) can significantly change the functional properties of involved receptors. Various biochemical and biophysical methodologies have been developed in the last two decades to identify and functionally evaluate GPCR heteromers in heterologous cells, with recent approaches focusing on GPCR complex stoichiometry and stability. Yet validation of these observations in native tissues is still lagging behind for the majority of GPCR heteromers. Remarkably, recent studies, particularly some involving advanced fluorescence microscopy techniques, are contributing to our current knowledge of aspects that were not well known until now, such as GPCR complex stoichiometry and stability. In parallel, a growing effort is being applied to move the field forward into native systems. This short review will highlight recent developments to study the stoichiometry and stability of GPCR complexes and methodologies to detect native GPCR dimers.

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“…3 Then, under diabetic/obesity conditions, endotheliumderived vasodilators may increase their participation as a counter-regulatory mechanism towards homeostasis including an increased participation vasodilator components of RAS as AT2R 4 or angiotensin-converting enzyme 2 (ACE2)-angiotensin 1-7. [5][6][7] Additionally, damage produced by metabolic disturbances can change adrenergic or Ang II receptors functionality, increasing the crosstalk between α 1 and AT1 receptors. [8][9][10][11] Indeed, an increased α 1 /AT1 crosstalk has been proposed as an early damage indicator of metabolic disturbances.…”

Section: Introductionmentioning

confidence: 99%

Evidence of changes in alpha-1/AT1 receptor function generated by diet-induced obesity

Juárez

Tufiño

Querejeta

et al. 2017

Diabetes and Vascular Disease Research

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To study whether hypercaloric diet-induced obesity deteriorates vascular contractility of rat aorta through functional changes in α adrenergic and/or AT1 Angiotensin II receptors. Angiotensin II- or phenylephrine-induced contraction was tested on isolated aorta rings with and without endothelium from female Wistar rats fed for 7 weeks with hypercaloric diet or standard diet. Vascular expression of Angiotensin II Receptor type 1 (AT1R), Angiotensin II Receptor type 2 (AT2R), Cyclooxygenase-1 (COX-1), Cyclooxygenase-2 (COX-2), inducible Nitric Oxide Synthase (iNOS) and endothelial Nitric Oxide Synthase (eNOS), as well as blood pressure, glucose, insulin and angiotensin II blood levels were measured. Diet-induced obesity did not significantly change agonist-induced contractions (Emax and pD hypercaloric diet vs standard diet n.s.d.) of both intact (e+) or endothelium free (e-) vessels but significantly decrease both phenylephrine and angiotensin II contraction (Emax p < 0.01 hypercaloric diet vs standard diet) in the presence of both prazosin and losartan but only in endothelium-intact vessels. Diet-induced obesity did not change angiotensin II AT1, AT2 receptor proteins expression but reduced COX-1 and NOS2 ( p < 0.05 vs standard diet). Seven-week hypercaloric diet-induced obesity produces alterations in vascular adrenergic and angiotensin II receptor dynamics that suggest an endothelium-dependent adrenergic/angiotensin II crosstalk. These changes reflect early-stage vascular responses to obesity.

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Cross-talk with β2-adrenoceptors enhances ligand affinity properties from endothelial alpha1D-adrenoceptors that mediates carotid relaxation

Cited by 16 publications

References 35 publications

Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion in a Sheep Model: Critical Role of α1-Adrenergic Signaling

Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion in a Sheep Model: Critical Role of α1-Adrenergic Signaling

G Protein–Coupled Receptor Multimers: A Question Still Open Despite the Use of Novel Approaches

Evidence of changes in alpha-1/AT1 receptor function generated by diet-induced obesity

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