Heregulin upregulates the expression of nitric oxide synthase (NOS)-1 in rat cerebellar granule neurons via the ErbB4 receptor.

Heregulin plays key roles in regulating cell number, determining fate and establishing pattern in the developing nervous system via specific receptors (ErbBs), including ErbB4. Two recent reports have shown that ErbB4 forms a complex with postsynaptic density proteins, which are, in turn, known to complex with nitric oxide synthase (NOS)-1. To reveal whether heregulin might regulate the expression of NOS-1, cultures enriched in cerebellar granule cells were exposed to heregulin for 72 h. This treatment resulted in an increase in NOS-1 protein (> 70%), an effect mediated by the ErbB4 receptor. While nitric oxide might mediate some of the downstream effects of heregulin in the nervous system, heregulin treatment neither enhanced granule cell survival, nor protected neurons from acute glutamate excitotoxicity.