Ouabain modulates airway remodeling caused by Th2-high asthma in mice

Galvão, José Guilherme Ferreira Marques; Cavalcante‐Silva, Luiz Henrique Agra; Lima, Éssia de Almeida; Carvalho, Deyse Cristina Madruga; Alves, Adriano Francisco; Mascarenhas, Sandra Rodrigues

doi:10.1016/j.intimp.2022.108808

Cited by 7 publications

(1 citation statement)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(Regrettably, they did not compare cells from α2 R and α2 S mice to determine if the crucial factor was the ouabain binding site rather than α2 NKA itself.) IP ouabain also attenuates ovalbumin-induced acute airway inflammation and subsequent airway remodeling in a model of allergic asthma ( 532 , 533 ). Bufalin and MBG ( 534 – 536 ), and digoxin ( 510 , 537 ), too, reduce proinflammatory cytokines and exert an anti-inflammatory effect when administered IP in various mouse models including MI.…”

Section: The Physiology and Pathophysiology Of Cts-nka Interactionsmentioning

confidence: 99%

Sensational site: the sodium pump ouabain-binding site and its ligands

Blaustein,

Hamlyn

2024

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Cardiotonic steroids (CTS), used by certain insects, toads, and rats for protection from predators, became, thanks to Withering's trailblazing 1785 monograph, the mainstay of heart failure (HF) therapy. In the 1950's and 60's we learned that the CTS receptor was part of the sodium pump (NKA) and that the Na+/Ca2+ exchanger was critical for the acute cardiotonic effect of digoxin- and ouabain-related CTS. This "settled" view was upended by seven revolutionary observations. First, sub-nanomolar ouabain sometimes stimulates NKA whilst higher concentrations are invariably inhibitory. Second, endogenous ouabain (EO) was discovered in the human circulation. Third, in the DIG clinical trial, digoxin only marginally improved outcome in HF patients. Fourth, cloning of NKA in 1985 revealed multiple NKA α and β subunit isoforms that, in the rodent, differ in their sensitivities to CTS. Fifth, the NKA is a cation pump and a hormone receptor/signal transducer. EO binding to NKA activates, in a ligand- and cell-specific manner, several protein kinase and Ca2+-dependent signaling cascades that have widespread physiological effects and can contribute to hypertension and HF pathogenesis. Sixth, all CTS are not equivalent: e.g., ouabain induces hypertension in rodents while digoxin is anti-hypertensinogenic ("biased signaling"). Seventh, most common rodent hypertension models require a highly ouabain-sensitive α2 NKA and the elevated blood pressure is alleviated by EO immunoneutralization. These numerous activities are enabled by NKA's intricate structure. We have just begun to understand the endocrine role of the endogenous ligands and the broad impact of the ouabain binding site on physiology and pathophysiology.

show abstract