Journal of Neuroscience, Vol 10, 1479-1485, Copyright © 1990 by Society for Neuroscience
Purine analogs inhibit nerve growth factor-promoted neurite outgrowth by sympathetic and sensory neurons
LA Greene, C Volonte and A Chalazonitis
Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Past studies have shown that purine analogs block certain, but not all,
responses of cultured rat PC12 pheochromocytoma cells to nerve growth
factor (NGF). In the present work, newborn rat sympathetic and sensory
neurons were exposed to NGF in the presence or absence of the purine
analogs 6-thioguanine and 2-aminopurine. These compounds reversibly
suppressed NGF-dependent neurite outgrowth by the neurons and did so at
concentrations comparable to those effective on PC12 cells. In contrast to
their effects on neurites, neither compound significantly blocked
NGF-promoted neuronal survival. Similar effects were seen with cultures of
chick embryo sympathetic ganglia. These findings show that purine analog
effects on NGF responses can be extended to mammalian and avian neurons.
Moreover, the differential effects of the analogs on neurite outgrowth and
survival indicate that these 2 actions of NGF can be dissected from one
another and may represent different mechanistic pathways.