Protease-activated receptor-2-mediated inhibition of ion transport in human bronchial epithelial cells

A cytoprotective role for protease-activated receptor-2 (PAR2) has been sug gested in a number of systems including the airway, and to this end, we hav e studied the role that PARs play in the regulation of airway ion transport , using cultures of normal human bronchial epithelial cells. PAR2 activator s, added to the basolateral membrane, caused a transient, Ca2+-dependent in crease in short-circuit current (I-sc), followed by a sustained inhibition of amiloride- sensitive I-sc. These phases corresponded with a transient in crease in intracellular Ca2+ concentration and then a transient increase, f ollowed by decrease, in basolateral K+ permeability. After PAR2 activation and the addition of amiloride, the forskolin-stimulated increase in Isc was also attenuated. By contrast, PAR2 activators added to the apical surface of the epithelia or PAR1 activators added to both the apical and basolatera l surfaces were without effect. PAR2 may, therefore, play a role in the air way, regulating Na+ absorption and anion secretion, processes that are cent ral to the control of airway surface liquid volume and composition.