Specific down-regulation of the alpha-bungarotoxin binding component on chick autonomic neurons by ciliary...

Chick ciliary ganglion neurons have a cholinergic membrane component that binds alpha-bungarotoxin with high affinity but has no known function. The component is different from the nicotinic ACh receptor on the neurons that mediates cholinergic transmission through the ganglion. Ciliary neuronotrophic factor (CNTF) has been shown to enhance the survival of ciliary ganglion neurons in cell culture and has been postulated to act as a target-derived trophic factor for the neurons in vivo. We show here that a factor indistinguishable from CNTF specifically down-regulates alpha-bungarotoxin binding sites on the neurons while increasing cell growth and the number of ACh receptors on the cells. Similar effects, though reduced in magnitude, are seen with chick sympathetic neurons. CNTF has no effect on the number of ACh receptors found on chick myotubes in culture. The down-regulation of alpha-bungarotoxin binding sites on neurons caused by CNTF occurs with a half-time of about 19 hr and is largely reversed within a 4 d period following CNTF removal. It is distinct from the down-regulation caused by cholinergic agonists. Nerve growth factor and fibroblast growth factor have no apparent effect on the number of alpha-bungarotoxin binding sites on the neurons, though fibroblast growth factor does stimulate neuronal growth. The results indicate that the effects of CNTF on the alpha-bungarotoxin binding component are both novel for a growth factor and specific, and they suggest a relationship between the component and the regulation of growth by the target tissue.