Extracellular ATP modulates ion transport via P2Y purinoceptors in a middle-ear epithelial cell line.

Abstract

Mucus and cellular debris are eliminated from the middle-ear cavity through the E-tube by the mucociliary system. Depth of the periciliary fluid layer is thought to be regulated by epithelial ion transport activity. Since impairment of the mucociliary system is a key step in the development of otitis media with effusion, we investigated the ion transport mechanisms of the middle-ear epithelium using the middle-ear MESV cell line. ATP has been shown to modulate ion transport as well as various cellular functions in several cell types via purinoceptors. In order to investigate a possible modulation of the transport activity of MESV cells, we evaluated short-circuit current (Isc) changes in response to specific stimulation of putative purinoceptors by ATP and its various analogs. ATP dramatically increased Isc, while adenosine had no effect, thus demonstrating the presence of P2 receptors according to the original classification by Burnstock. The rank order of potency of purinoceptor agonists for stimulation of Isc on the apical side (ATP > UTP > gamma-SATP >> beta-SADP > 2-methylthio-ATP, 2MeSATP > beta, gamma-methylene-ATP, beta,gamma-MeATP) and on the basolateral side (ATP > gamma-SATP > UTP >> beta-SADP > 2 MeSATP > beta,gamma-MeATP), along with studies using selective antagonists and intracellular calcium measurements are consistent with a P2Y receptor subtype. The ATP-induced increase in Isc was related to sodium transport. This modulation might be of importance in stress conditions such as inflammation.