Adenosine closes the K+ channel KCa3.1 in human lung mast cells and inhibits their migration via the adenosine A2A receptor.

摘要: Human lung mast cells (HLMC) express the Ca2+-activated K+ channel KCa3.1, which opens following IgE-dependent activation. This hyperpolarises cell membrane and potentiates both Ca2+ influx degranulation. In addition, blockade of KCa3.1 profoundly inhibits HLMC migration to a variety diverse chemotactic stimuli. activation is attenuated by β2adrenoceptor through Gαs-coupled mechanism independent cyclic AMP. Adenosine an important mediator that attenuates enhances release A2A A2B adenosine receptors, respectively. We show at concentrations inhibit degranulation (10–5–10–3 M), closes dose-dependently reversibly. suppression was reversed partially selective receptor antagonist ZM241385 but not MRS1754, effects were mimicked agonist CGS21680. also opened depolarising current carried non-selective cations. As predicted from role in migration, abolished chemotaxis asthmatic airway smooth muscle-conditioned medium. summary, providing clearly defined agonists with channel-modulating function may be useful for treatment cell-mediated disease.