Functional characterization of heterotrimeric G-proteins in rat diaphragm muscle

Andrade-Lopes, Ana Luiza; Pires-Oliveira, Marcelo; Rodrigues, Francisco Sandro Menezes; Godinho, Rosely Oliveira

doi:10.1016/j.resp.2010.11.005

Cited by 5 publications

(5 citation statements)

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“…At low concentrations, ␤ 2 -AR agonists induce a more sustained increase in twitch contraction (Figs. 1A and 2A), supporting the preferential coupling of ␤ 2 -AR to G s protein in skeletal muscle (Andrade-Lopes et al, 2011). On the other hand, secondary coupling of ␤ 2 -AR to G i protein would be accountable for either the descending phase of the ␤ 2 -ARpositive inotropic response, observed after persistent (Ն30 min) activation of ␤ 2 -AR with low to intermediary concentrations of agonists or reduced inotropic response at a high concentration of clenbuterol or fenoterol (Ն100 nM).…”

Section: Discussionsupporting

confidence: 55%

“…Endogenous sympathomimetic amines or synthetic ␤-adrenoceptor (␤-AR) agonists, such as nonselective isoproterenol (Bowman and Nott, 1969;AndradeLopes et al, 2011) or ␤ 2 -AR-selective salbutamol (Easton et al, 2008) increase muscle contraction force via activation of stimulatory G protein (G s )-coupled receptors (GPCRs), which in turn activates adenylyl cyclases (ACs). The sequential increase in intracellular cAMP (Bowman and Nott, 1969;Cairns and Dulhunty, 1993;Andrade-Lopes et al, 2011) and activation of protein kinase A result in phosphorylation of ryanodine receptors and increased Ca 2ϩ release from the sarcoplasmic reticulum (Reiken et al, 2003;Lynch and Ryall, 2008), which culminates in potentiation of muscle contraction. However, in many cells, ␤-AR/G s /AC-mediated responses are affected by promiscuous coupling of ␤-AR to other G␣ subunits, especially with the inhibitory G␣ i subfamily as reported in Sf9 insect cells overexpressing ␤ 2 -AR (Wenzel-Seifert and Seifert, 2000) and human embryonic kidney 293 cells (Daaka et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Contribution of the Extracellular cAMP-Adenosine Pathway to Dual Coupling of β₂-Adrenoceptors to G_sand G_iProteins in Mouse Skeletal Muscle

Duarte

Rodrigues

Godinho

2012

J Pharmacol Exp Ther

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␤ 2 -Adrenoceptor (␤ 2 -AR) agonists increase skeletal muscle contractile force via activation of G s protein/adenylyl cyclases (AC) and increased generation of cAMP. Herein, we evaluated the possible dual coupling of ␤ 2 -AR to G s and G i proteins and the influence of the ␤ 2 -AR/G s -G i /cAMP signaling cascade on skeletal muscle contraction. Assuming that the increment of intracellular cAMP is followed by cAMP efflux and extracellular generation of adenosine, the contribution of the extracellular cAMP-adenosine pathway on the ␤ 2 -AR inotropic response was also addressed. The effects of clenbuterol/fenoterol (␤ 2 -AR agonists), forskolin (AC activator), cAMP/8-bromo-cAMP, and adenosine were evaluated on isometric contractility of mouse diaphragm muscle induced by supramaximal direct electrical stimulation (0.1 Hz, 2 ms duration). Clenbuterol/fenoterol (10 -1000 M), 1 M forskolin, and 20 M rolipram induced transient positive inotropic effects that peaked 30 min after stimulation onset, declining to 10 to 20% of peak levels in 30 min.The late descending phase of the ␤ 2 -AR agonist inotropic effect was mimicked by either cAMP or adenosine and abolished by preincubation of diaphragm with pertussis toxin (PTX) (G i signaling inhibitor) or the organic anion transporter inhibitor probenecid, indicating a delayed coupling of ␤ 2 -AR to G i protein which depends on cAMP efflux. Remarkably, the PTX-sensitive ␤ 2 -AR inotropic effect was inhibited by the A 1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine and ecto-5Ј-phosphodiesterase inhibitor ␣,␤-methyleneadenosine 5Ј-diphosphate sodium salt, indicating that ␤ 2 -AR coupling to G i is indirect and dependent on A 1 receptor activation. The involvement of the extracellular cAMP-adenosine pathway in ␤ 2 -AR signaling would provide a negative feedback loop that may limit stimulatory G protein-coupled receptor positive inotropism and potential deleterious effects of excessive contractile response.

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Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Contribution of the Extracellular cAMP-Adenosine Pathway to Dual Coupling of β₂-Adrenoceptors to G_sand G_iProteins in Mouse Skeletal Muscle

Duarte

Rodrigues

Godinho

2012

J Pharmacol Exp Ther

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“…However, the effect and mechanism of H 2 S in diaphragm dysfunction have not been fully elucidated. Rat skeletal muscle cell line L6 has been widely used to study the regeneration and function of skeletal muscle [ 50 – 52 ]. LPS, a major constituent of the cell wall of Gram-negative bacteria, is a potent agent widely used to model bacterial challenges of mammalian cells [ 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide Alleviates Lipopolysaccharide‐Induced Diaphragm Dysfunction in Rats by Reducing Apoptosis and Inflammation through ROS/MAPK and TLR4/NF‐κB Signaling Pathways

Zhang

Lü

Duan

et al. 2018

Oxidative Medicine and Cellular Longevity

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Diaphragm dysfunction is an important clinical problem worldwide. Hydrogen sulfide (H2S) is involved in many physiological and pathological processes in mammals. However, the effect and mechanism of H2S in diaphragm dysfunction have not been fully elucidated. In this study, we detected that the level of H2S was decreased in lipopolysaccharide- (LPS-) treated L6 cells. Treatment with H2S increased the proliferation and viability of LPS-treated L6 cells. We found that H2S decreased reactive oxygen species- (ROS-) induced apoptosis through the mitogen-activated protein kinase (MAPK) signaling pathway in LPS-treated L6 cells. Administration of H2S alleviated LPS-induced inflammation by mediating the toll-like receptor-4 (TLR-4)/nuclear factor-kappa B (NF-κB) signaling pathway in L6 cells. Furthermore, H2S improved diaphragmatic function and structure through the reduction of inflammation and apoptosis in the diaphragm of septic rats. In conclusion, these findings indicate that H2S ameliorates LPS-induced diaphragm dysfunction in rats by reducing apoptosis and inflammation through ROS/MAPK and TLR4/NF-κB signaling pathways. Novel slow-releasing H2S donors can be designed and applied for the treatment of diaphragm dysfunction.

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“…It is well accepted that the cAMP signaling pathway mediates the biological action of many endogenous substances or synthetic drugs (e.g., catecholamines and ␤ 2 -adrenoceptor agonists) via receptor-activated G s proteins (GsPCR) (1,7,15,18,21,23,46,51).…”

Section: Discussionmentioning

confidence: 99%

The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes

Bergantin

Figueiredo

Godinho

2011

Journal of Applied Physiology

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Bergantin LB, Figueiredo LB, Godinho RO. The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes. J Appl Physiol 111: 1710 -1718, 2011. First published September 15, 2011 doi:10.1152/japplphysiol.00586.2011.-The molecular regulation of skeletal muscle proteolysis and the pharmacological screening of anticatabolic drugs have been addressed by measuring tyrosine release from prepubertal rat skeletal muscles, which are thin enough to allow adequate in vitro diffusion of oxygen and substrates. However, the use of muscle at accelerated prepubertal growth has limited the analysis of adult muscle proteolysis or that associated with aging and neurodegenerative diseases. Here we established the adult rat lumbrical muscle (4/hindpaw; 8/rat) as a new in situ experimental model for dynamic measurement of skeletal muscle proteolysis. By incubating lumbrical muscles attached to their individual metatarsal bones in Tyrode solution, we showed that the muscle proteolysis rate of adult and aged rats (3-4 to 24 mo old) is 45-25% of that in prepubertal animals (1 mo old), which makes questionable the usual extrapolation of proteolysis from prepubertal to adult/senile muscles. While acute mechanical injury or 1-to 7-day denervation increased tyrosine release from adult lumbrical muscle by up to 60%, it was reduced by 20 -28% after 2-h incubation with ␤-adrenoceptor agonists, forskolin or phosphodiesterase inhibitor IBMX. Using inhibitors of 26S-proteasome (MG132), lysosome (methylamine), or calpain (E64/leupeptin) systems, we showed that ubiquitin-proteasome is accountable for 40 -50% of total lumbrical proteolysis of adult, middle-aged, and aged rats. In conclusion, the lumbrical model allows the analysis of muscle proteolysis rate from prepubertal to senile rats. By permitting eight simultaneous matched measurements per rat, the new model improves similar protocols performed in paired extensor digitorum longus (EDL) muscles from prepubertal rats, optimizing the pharmacological screening of drugs for anticatabolic purposes.

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Functional characterization of heterotrimeric G-proteins in rat diaphragm muscle

Cited by 5 publications

References 50 publications

Contribution of the Extracellular cAMP-Adenosine Pathway to Dual Coupling of β₂-Adrenoceptors to G_sand G_iProteins in Mouse Skeletal Muscle

Contribution of the Extracellular cAMP-Adenosine Pathway to Dual Coupling of β₂-Adrenoceptors to G_sand G_iProteins in Mouse Skeletal Muscle

Hydrogen Sulfide Alleviates Lipopolysaccharide‐Induced Diaphragm Dysfunction in Rats by Reducing Apoptosis and Inflammation through ROS/MAPK and TLR4/NF‐κB Signaling Pathways

The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes

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Functional characterization of heterotrimeric G-proteins in rat diaphragm muscle

Cited by 5 publications

References 50 publications

Contribution of the Extracellular cAMP-Adenosine Pathway to Dual Coupling of β2-Adrenoceptors to Gsand GiProteins in Mouse Skeletal Muscle

Contribution of the Extracellular cAMP-Adenosine Pathway to Dual Coupling of β2-Adrenoceptors to Gsand GiProteins in Mouse Skeletal Muscle

Hydrogen Sulfide Alleviates Lipopolysaccharide‐Induced Diaphragm Dysfunction in Rats by Reducing Apoptosis and Inflammation through ROS/MAPK and TLR4/NF‐κB Signaling Pathways

The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes

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Contribution of the Extracellular cAMP-Adenosine Pathway to Dual Coupling of β₂-Adrenoceptors to G_sand G_iProteins in Mouse Skeletal Muscle

Contribution of the Extracellular cAMP-Adenosine Pathway to Dual Coupling of β₂-Adrenoceptors to G_sand G_iProteins in Mouse Skeletal Muscle