Extracellular ATP regulation of airway secretion

Abstract

Both the superficial epithelium and submucosal glands play a role in airway secretion. Electrophysiological experiments showed that extracellular ATP induced an initial transient increase in Cl -secretion followed by a prolonged inhibition of Na + absorption in rabbit tracheal epithelium, which lacks submucosal glands. The response to ATP was mimicked by UTP or ATPγS in untreated normal epithelium, suggesting a P 2U -type receptor in the epithelium. Meanwhile, in tracheal epithelium from SO 2 -induced bronchitic rabbit ATP induced a prolonged increase in Cl -secretion without a decrease in Na + absorption, which was mimicked by adenosine or isoproterenol (ISP). The alteration in the bronchitic epithelium was shown to result from a newly expressed CFTR by both immunohistological and Northern blot analysis. Patch-clamp experiments showed that ATP induced an initial Cl -current followed by K + current in acinar cells of submucosal glands isolated from feline and human trachea. Although ISP alone or adenosine did not evoke any significant current responses, ISP augmented the ATP-induced Cl -and K + currents. A phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), mimicked the augmentation by ISP. ATP also induced an increase in [Ca 2+ ] i in acinar cells of submucosal glands, which was augmented by ISP. Mucus glycoprotein (MGP) secretion from isolated submucosal glands was also stimulated by ATP but not by adenosine. The ATP-induced MGP secretion was augmented by ISP. These findings suggest that P 2 -receptor stimulation and the resultant [Ca 2+ ] i -rise induce both electrolyte and MGP secretion, which is enhanced by [cAMP] i -rise in airway submucosal glands. Drug Dev.

Purinergic Signaling in the Airways

“…A number of reviews on different aspects of purinergic signaling in the airways are available: extracellular purinergic regulation of airways secretion and ciliary activity (Braiman et al, 2000;Rooney, 2001;Shimura, 2001;Leipziger, 2003;Schwiebert and Zsembery, 2003;Davis and Lazarowski, 2008;Barth and Kasper, 2009;Lazarowski and Boucher, 2009;Dietl et al, 2010); nervous control of the airways (Burnstock, 1988;Wegner, 2001;Brouns et al, 2006;Taylor-Clark and Undem, 2006;Funk et al, 2008); purinergic signaling in airway diseases (Ahmad et al, 2006;Spicuzza et al, 2006;Ackland et al, 2007); and pulmonary vasculature (Liu and Barnes, 1994). Here, we intend to provide a more comprehensive overview of airway-related purinergic signaling.…”