Apical and basolateral atp stimulate tracheal epithelial chloride secretion via multiple purinergic receptors and signaling pathways. Hwang, Tae-Ho, Erik M. Schwiebert, and William B. Guggino. Departments of Physiology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD
APStracts 2:0429C, 1995.
Stimulation of chloride (Cl-) secretion across the airway epithelium by ATP or UTP as agonists has therapeutic implications for cystic fibrosis. Our results demonstrate that ATP stimulates Cl- secretion in rat tracheal epithelial cell monolayers in primary culture from the apical or basolateral side of the monolayer. Multiple types of ATP-sensitive Cl- conductances in intact monolayers were elucidated through inhibition by Cl- channel blocking drugs. Multiple Cl- conductances stimulated by ATP and cAMP (tested for comparison) were also deciphered more specifically by nystatin permeabilization of the basolateral membrane, subsequent imposition of symmetrical Cl-, I-, or Br- solutions to test halide permselectivity, inhibition by Cl- channel blocking drugs, and construction of current-voltage (I-V) plots to study time- and voltage-dependence of the currents. Apical ATP stimulates Cl- secretion through P2U (or P2Y2) purinergic receptors via both Ca2+i-dependent and Ca2+i-independent signaling pathways by opening outwardly rectifying chloride channels (ORCCs), CFTR Cl- channels, and Ca2+i-dependent Cl- channels (CaCCs). Basolateral ATP stimulates Cl- secretion via a combination of receptor subtypes (P2T and P2U) or a novel type of receptor (P2Y3) independent of Ca2+i or cAMP signaling by opening only CFTR channels. Cyclic AMP also stimulated multiple types of Cl- conductances, consistent with simultaneous activation of CFTR and ORCCs. Taken together, these results suggest that ATP as an agonist stimulates Cl- secretion via multiple purinergic receptors and multiple signal transduction pathways activated in different membrane domains of tracheal epithelia. 

Received 23 August 1995; accepted in final form 20 November 1995.
APS Manuscript Number C523-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95