PLATELET-ACTIVATING-FACTOR MAY STIMULATE BOTH RECEPTOR-DEPENDENT AND RECEPTOR-INDEPENDENT INCREASES IN [CA2-CELLS(] IN HUMAN AIRWAY EPITHELIAL)

Platelet-activating factor (PAF) is a potent mediator which produces a wide range of biological responses by binding to specific, high affin ity receptors on the target cell surface. In addition, we and others h ave observed cellular responses to PAF which are not receptor-mediated . We report here that in HBE-16 human bronchial epithelial cells, PAF produces a biphasic increase in [Ca2+](i) consisting of a rapid initia l increase due to release from intracellular stores followed by a grad ual, sustained phase caused by influx of extracellular Ca2+. Under cer tain conditions, the PAF receptor antagonist L-659,989 completely bloc ks the release of Ca2+ from intracellular stores, suggesting a complet e block of the receptor-mediated response. Under these same conditions , a residual influx of extracellular Ca2+ is observed, suggesting a po ssible receptor-independent response. HBE-16 cells partially metaboliz e PAF to 1-O-alkyl-2 acetyl-sn-glycerol (AAG), a bioactive diacylglyce rol analog. Moreover, AAG stimulates Ca2+ influx in these cells; the r esponse to AAG is at least 100-fold more potent than that to PAF. Take n together, these results suggest that PAF may stimulate Ca2+ influx i n HBE-16 cells through a receptor-independent pathway mediated by AAG. Thus these studies suggest a previ ously unrecognized dual-pathway re gulatory mechanism for PAF in the airway.