In:
American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 278, No. 4 ( 2000-04-01), p. L726-L736
Abstract:
ATP induced a biphasic increase in the intracellular Ca 2+ concentration ([Ca 2+ ] i ), an initial spike, and a subsequent plateau in A549 cells. Erythromycin (EM) suppressed the ATP-induced [Ca 2+ ] i spike but only in the presence of extracellular calcium ([Formula: see text]). It was ineffective against ATP- and UTP-induced inositol 1,4,5-trisphosphate [Ins(1,4,5) P 3 ] formation and UTP-induced [Ca 2+ ] i spike, implying that EM perturbs Ca 2+ influx from the extracellular space rather than Ca 2+ release from intracellular Ca 2+ stores via the G protein-phospholipase C-Ins(1,4,5) P 3 pathway. A verapamil-sensitive, KCl-induced increase in [Ca 2+ ] i and the Ca 2+ influx activated by Ca 2+ store depletion were insensitive to EM. 3′- O-(4-benzoylbenzoyl)-ATP evoked an[Formula: see text]-dependent [Ca 2+ ] i response even in the presence of verapamil or the absence of extracellular Na + , and this response was almost completely abolished by EM pretreatment. RT-PCR analyses revealed that P2X 4 as well as P2Y 2 , P2Y 4 , and P2Y 6 are coexpressed in this cell line. These results suggest that in A549 cells 1) the coexpressed P2X 4 and P2Y 2 /P2Y 4 subtypes contribute to the ATP-induced [Ca 2+ ] i spike and 2) EM selectively inhibits Ca 2+ influx through the P2X channel. This action of EM may underlie its clinical efficacy in the treatment of airway inflammation.
Type of Medium:
Online Resource
ISSN:
1040-0605
,
1522-1504
DOI:
10.1152/ajplung.2000.278.4.L726
Language:
English
Publisher:
American Physiological Society
Publication Date:
2000
detail.hit.zdb_id:
1477300-4
SSG:
12
