Publications by authors named "T Alkawadri"

Cholinergic tone is elevated in obstructive lung conditions such as COPD and asthma, but the cellular mechanisms underlying cholinergic contractions of airway smooth muscle (ASM) are still unclear. Some studies report an important role for L-type Ca channels (LTCC) and Ano1 Ca-activated Cl™ channels (CACC) in these responses, but others dispute their importance. Cholinergic contractions of ASM involve activation of M3Rs, however stimulation of M2Rs exerts a profound hypersensitisation of these responses.

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Malfunctions in airway smooth muscle Ca-signalling leads to airway hyperresponsiveness in asthma and chronic obstructive pulmonary disease. Ca-release from intracellular stores is important in mediating agonist-induced contractions, but the role of influx via l-type Ca channels is controversial. We re-examined roles of the sarcoplasmic reticulum Ca store, refilling of this store via store-operated Ca entry (SOCE) and l-type Ca channel pathways on carbachol (CCh, 0.

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We investigated effects of TMEM16A blockers benzbromarone, MONNA, CaCCA01 and Ani9 on isometric contractions in mouse bronchial rings and on intracellular calcium in isolated bronchial myocytes. Separate concentrations of carbachol (0.1-10 μM) were applied for 10 min periods to bronchial rings, producing concentration-dependent contractions that were well maintained throughout each application period.

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Article Synopsis
  • Beta-adrenoceptor agonists, particularly β1-ARs, inhibit contractions of airway smooth muscle (ASM) that are primarily driven by cholinergic mechanisms, highlighting the complex interplay between M2 and M3 muscarinic receptors in this process.
  • Recent findings show that M2 receptors can enhance M3 receptor activity during cholinergic contractions, indicating they play a significant role beyond just counteracting β-AR relaxation effects.
  • The study demonstrated that β1-AR agonist denopamine effectively reduces electric field stimulation-evoked contractions in ASM, with diminished effects in mice lacking M2 receptors, suggesting that M2Rs are crucial for the responsiveness of ASM to β-AR activation.
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Postjunctional M2Rs on airway smooth muscle (ASM) outnumber M3Rs by a ratio of 4:1 in most species, however, it is the M3Rs that are thought to mediate the bronchoconstrictor effects of acetylcholine. In this study, we describe a novel and profound M2R-mediated hypersensitization of M3R-dependent contractions of ASM at low stimulus frequencies..

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