EPITHELIAL cells exist in a complex setting in which responses to muco
sal or serosal environments are mediated by receptors expressed on spe
cialized cellular domains, such as apical versus basolateral cell memb
ranes, We investigated whether airway epithelia can react selectively
through G-protein-coupled receptors to stimuli in the mucosal or seros
al environments by measuring inositol phosphate and intracellular Ca2 responses in polarized human nasal epithelial monolayers, We report h
ere that unilateral ATP (10(-4) M) administration stimulated P-2 purin
oceptors and tapped pools of intracellular Ca2+ associated with the pl
asma membrane ipsilateral but not contralateral to stimulated receptor
s. Similarly, activation of plasma membrane Ca2+ influx by ATP was con
fined to the membrane ipsilateral to receptor stimulation. These findi
ngs demonstrate that polarized epithelia restrict P-2 receptor-mediate
d responses to a single domain of the cell, reflecting membrane-specif
ic generation and catabolism of inositol phosphates and confinement of
calcium influx regulation to the membrane ipsilateral to the stimulat
ed receptors.