Extracellular ATP regulation of airway secretion

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 st Na+ absorption in rabbit tracheal epithelium, which lacks submucosal glands. The response to ATP was mimicked by UTP or ATP gammaS in untreated normal epithelium, suggesting a P-2U-type receptor in the epithelium, Meanwhile, in tracheal epithelium from SO2-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 along 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 [Ca2+](i) in acinar cells of submucosal glands, which was augmented by ISP. Mucus glycoprotein (MCP) secretion from isolated submucosal glands was also stimulated by ATP but not by adenosine. The ATP-induced MCP secretion was augmented by ISP. These findings suggest that P-2-receptor stimulation and the resultant [Ca2+](i)-rise induce both electrolyte and MGP secretion, which is enhanced by [cAMP](i)-rise in airway submucosal glands. Drug Dev Res. 52:170-177, 2001. (C) 2001 Wiley-Liss, Inc.