Impact of the cAMP efflux and extracellular cAMP-adenosine pathway on airway smooth muscle relaxation induced by formoterol and phosphodiesterase inhibitors

Satori, Naiara Ayako; Pacini, Enio Setsuo Arakaki; Godinho, Rosely Oliveira

doi:10.1016/j.cbi.2023.110630

Cited by 6 publications

(5 citation statements)

References 43 publications

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“…RNA-sequencing was used to understand multifaceted mechanisms in rats with asthma [ 26 ]. We measured mRNA expression of each sample in control and asthma groups.…”

Section: Resultsmentioning

confidence: 99%

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Analysis of global gene expression using RNA-sequencing reveals novel mechanism of Yanghe Pingchuan decoction in the treatment of asthma

Pan,

He,

Gong

et al. 2024

BMC Pulm Med

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Background Yanghe Pingchuan decoction (YPD) has been used for asthma treatment for many years in China. We sought to understand the mechanism of YPD, and find more potential targets for YPD-based treatment of asthma. Methods An ovalbumin-induced asthma model in rats was created. Staining (hematoxylin and eosin, Masson) was used to evaluate the treatment effect of YPD. RNA-sequencing was carried out to analyze global gene expression, and differentially expressed genes (DEGs) were identified. Analysis of the functional enrichment of genes was done using the Gene Ontology database (GO). Analysis of signaling-pathway enrichment of genes was done using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Real-time reverse transcription-quantitative polymerase chain reaction was undertaken to measure expression of DEGs. Results Pathology showed that YPD had an improvement effect on rats with asthma. RNA-sequencing showed that YPD led to upregulated and downregulated expression of many genes. The YPD-based control of asthma pathogenesis may be related to calcium ion (Ca2+) binding, inorganic cation transmembrane transporter activity, microtubule motor activity, and control of canonical signaling (e.g., peroxisome proliferator-activated receptor, calcium, cyclic adenosine monophosphate). Enrichment analyses suggested that asthma pathogenesis may be related to Ca2 + binding and contraction of vascular smooth muscle. A validation experiment showed that YPD could reduce the Ca2 + concentration by inhibiting the Angiopoietin-II (Ang-II)/Phospholipase (PLA)/calmodulin (CaM0 signaling axis. Conclusion Control of asthma pathogenesis by YPD may be related to inhibition of the Ang-II/PLA/CaM signaling axis, reduction of the Ca2+ concentration, and relaxation of airway smooth muscle (ASM).

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“…RNA-sequencing was used to understand multifaceted mechanisms in rats with asthma [ 26 ]. We measured mRNA expression of each sample in control and asthma groups.…”

Section: Resultsmentioning

confidence: 99%

“…The current strategy to control an acute attack of asthma is to relax ASM and dilate the bronchus [ 26 ]. Ca 2+ regulation is crucial to the contraction and relaxation of ASM [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of global gene expression using RNA-sequencing reveals novel mechanism of Yanghe Pingchuan decoction in the treatment of asthma

Pan,

He,

Gong

et al. 2024

BMC Pulm Med

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“…Smooth muscle is the main tissue that plays an important role in asthmatic pathways that involve bronchoconstriction processes, bronchial hyper-reactivity, and airway remodeling [17].…”

Section: Relaxant Effectmentioning

confidence: 99%

“…Drugs Drug Candidates 2024, 3, FOR PEER REVIEW 6 verse-mode Na + /Ca 2+ exchangers and/or NO/cGMP system activation; and the augmented production of cGMP on rat trachea, which interferes with the contraction mechanism of smooth muscle cells in the airways (Scheme 4) [8,15,17]. With the obtained results, we cannot establish an SAR pattern with the number of compounds studied, nor due to the substituents included because of their great structural variation, but we can attribute it to the similarity between the 2-pyridones and 4Hpyrans with the 1,4-dihydropyridines, such as nifedipine.…”

Section: Relaxant Effectmentioning

confidence: 99%

“…Therefore, the mechanisms of relaxation of 1,6-dihydropyridine derivatives could be related with different pathways, such as β2-adrenergic stimulation that increases intracellular cyclic AMP (by adenylate cyclase activation) and induces ASM relaxation by protein kinase A activation. Other mechanisms involved are K+-channel opening, which causes the entry of K + and blocks the Ca 2+ channels, inducing hyperpolarization with consequent relaxation; cAMP increment by PDE4-phosphodiesterase inhibition; leukotriene and muscarinic receptor antagonism; Ca 2+ channel blockade, including the voltage-operated calcium channel (VOC), receptor-operated Ca 2+ channels (ROC), and reverse-mode Na + /Ca 2+ exchangers and/or NO/cGMP system activation; and the augmented production of cGMP on rat trachea, which interferes with the contraction mechanism of smooth muscle cells in the airways (Scheme 4) [8,15,17].…”

Section: Relaxant Effectmentioning

confidence: 99%

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Relaxant Activity of 4H-Pyran and 1,6-Dihydropyridine Derivatives on Isolated Rat Trachea

Estrada-Soto,

Alemán-Pantitlán,

Gaona-Tovar

et al. 2024

DDC

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Derivatives of 4H-pyrans and 1,6-dihydropyridines have generated considerable attention due to their interesting biological and therapeutic values. Their pharmacological activities include vasorelaxant, anticarcinogenic, antimicrobial, and antioxidant activities. Thus, the aim of the current work is to determine the relaxant effect of synthesized 4H-pyran and 1,6-dihydropyridine derivatives with potential anti-asthmatic properties on the smooth muscle airway, with a possible Ca2+-channel blockade as a mechanism of action due to their analogy with 1,4-dihidropyridines. 4H-pyrans and 1,6-dihydropyridines were achieved using multicomponent reactions by microwave and conventional heating. Also, test samples were evaluated ex vivo to determine their relaxant effect on isolated rat tracheal rings pre-contracted with carbachol. All compounds evaluated showed a significant relaxant effect on carbachol-induced contraction in tracheal rat rings. Compounds 4b, 4e, 7a, and 8d were the most potent from the entire series and were also more potent than theophylline, used as a positive control. In conclusion, in the current work some relaxant compounds of the airway smooth muscle with potential to be developed as anti-asthmatic drugs were obtained.

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Extracellular nucleotides in smooth muscle contraction

Babou Kammoe,

Sévigny

2024

Biochemical Pharmacology

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Impact of the cAMP efflux and extracellular cAMP-adenosine pathway on airway smooth muscle relaxation induced by formoterol and phosphodiesterase inhibitors

Cited by 6 publications

References 43 publications

Analysis of global gene expression using RNA-sequencing reveals novel mechanism of Yanghe Pingchuan decoction in the treatment of asthma

Analysis of global gene expression using RNA-sequencing reveals novel mechanism of Yanghe Pingchuan decoction in the treatment of asthma

Relaxant Activity of 4H-Pyran and 1,6-Dihydropyridine Derivatives on Isolated Rat Trachea

Extracellular nucleotides in smooth muscle contraction

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