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It has previously been documented that Zn[sup 2+] inhibits TrkAmediated effects of NGF. To evaluate the ability of Zn[sup 2+] to attenuate the biological activities of NGF mediated by p75[sup NTR], we characterized the effects of this transition metal cation on both binding and the pro-apoptotic properties of the NGFp75[sup NTR] interaction. Binding of NGF to p75[sup NTR] displayed higher affinity in embryonic chick retinal cells than in PC12 cells. NGF induced apoptosis in dissociated cultures of chick neural retina. The addition of 100 µM Zn[sup 2+] inhibited binding and chemical cross-linking of [sup 125]I-NGF to p75[sup NTR], and also attenuated apoptosis mediated by this ligand-receptor interaction. These studies lead to the conclusion that Zn[sup 2+] antagonizes NGF/p75[sup NTR]-mediated signaling, suggesting that the effect of this transition metal cation can be either pro- or anti-apoptotic depending on the cellular context. [ABSTRACT FROM AUTHOR]