BLOCKING NERVE GROWTH-FACTOR BINDING TO THE P75 NEUROTROPHIN RECEPTORON SYMPATHETIC NEURONS TRANSIENTLY REDUCES TRKA ACTIVATION BUT DOES NOT AFFECT NEURONAL SURVIVAL

Nerve growth factor interacts with the trkA tyrosine kinase receptor a nd with the p75 neurotrophin receptor. It is clear that trkA mediates most, if nor all, of the stereotypical responses of sympathetic neuron s to nerve growth factor but the role of the p75 neurotrophin receptor is unclear. In this study, we have asked whether a functional interac tion between p75 neurotrophin receptor and trkA exists in primary symp athetic neurons by disrupting nerve growth factor binding to p75 neuro trophin receptor. Acute assays reveal that blocking antibodies directe d against p75 neurotrophin receptor reduce nerve growth factor-mediate d trkA tyrosine phosphorylation and reduce the amount of nerve growth factor which binds the trkA receptor. This reduction in trkA activity is relatively short-lived ia vitro and blocking antibodies to p75 neur otrophin receptor do not inhibit long-term survival of nerve growth fa ctor-dependent primary neurons. Together, these data indicate that p75 neurotrophin receptor and trkA interact within primary neurons to enh ance nerve growth factor binding to the trkA receptor under conditions of acute but not chronic nerve growth factor exposure. (C) 1997 IBRO. Published by Elsevier Science Ltd.