Role of nerve growth factor in the regulation of parotid cell differentiation induced by rat serum

The present study was undertaken to examine the factors that regulate rat serum (RS)- and nerve growth factor (NGF)-induced differentiation in a rat parotid acinar cell line. RS elicited extracellular signal-regulated kinase (ERK1/ERK2) activation within 5min, while cyclic AMP (cAMP) levels transiently rose after 6hr. RS also elicited a rise in amylase mRNA levels within 30min, which preceded the rise in amylase protein levels. A possible role for NGF was suggested by the findings that parotid cells express both TrkA and p75 receptors. The immunoreactivity of these NGF receptors was reduced during exposure to RS. Following prolonged incubation in RS when ERK activity subsided to near basal levels, NGF restored ERK1/ERK2 activity to the elevated level initially observed in RS. NGF was ineffective when cells were incubated in fetal bovine serum. NGF, when incubated in combination with the cAMP-generating neuropeptides, calcitonin gene-related peptide and vasoactive intestinal peptide, markedly enhanced the cellular amylase content produced by RS. We conclude that parotid cell differentiation arises from an activation of cell surface receptors by humoral factors in combination with NGF and cAMP-generating neuropeptides.