Ethanol exposure reduces the density of the low-affinity nerve growth factor receptor (p75) on pheochromocytoma (PC12) cells

Abstract

Although ethanol is detrimental to the developing nervous system, the mechanism(s) by which ethanol produces neuronal damage is (are) not clear. One potential mechanism is ethanol-induced inhibition of neurotrophic support. This study utilized an in vitro model, pheochromocytoma PC12 cells, to examine the effect of ethanol on the nerve growth factor (NGF) receptor. NGF binding studies indicated that ethanol exposure (400 mg/dl for 4 days) reduced the density of the low-affinity (p75) NGF receptor on PC12 cells, but had no effect on the density of the high-affinity NGF receptor. The equilibrium dissociation constants ( K d) for both the low-affinity and high-affinity NGF receptors were unaffected by ethanol. Low-affinity NGF binding is mediated by the p75 component of the NGF receptor. Quantification of p75 by immunoprecipitation revealed that ethanol reduced the level of p75 in PC12 cells. However, Northern analysis indicated that the p75 mRNA was not reduced by ethanol exposure, raising the possibilities that ethanol inhibited translation of p75 or incorporation of the p75 protein into the plasma membrane. This work is consistent with the hypothesis that ethanol's detrimental effects may be produced in part by inhibition of neurotrophic support at the receptor level.