Influence of epidermal growth factor on bovine pancreatic duct cell bicarbonate

BACKGROUND AND AIMS: Epidermal growth factor (EGF) is secreted in pancreatic juice and its receptor is expressed on pancreatic duct cells (PDCs), suggesting a physiological role which has yet to be defined. Here we examined the effects of EGF on bicarbonate production and carbonic anhydrase (CA) activity in a PDC explant model. METHODS: Bovine main PDCs were prepared and maintained in culture as explants. Levels of CA expression, phosphorylation, and enzymatic activity were measured in resting cells and compared to that of cells exposed to 10 nM secretin, 10 nM EGF, or both. Bicarbonate production was measured using the autoburette pH titration technique. RESULTS: CA protein levels were unchanged with any treatment, but enzyme activity increased by 180% with secretin treatment and was reduced by 54% with EGF. The combination treatment led to a synergistic increase 240% above basal. EGF alone did not affect bicarbonate secretion, but the normal increase observed with secretin stimulation (1.3 +/- 0.4 to 2.9 +/- 0.6 micromol/h/cm(2)) was abolished by acute EGF pretreatment. On the other hand, EGF pretreatment for 24 h significantly increased basal and stimulated secretion (2.2 +/- 0.5 and 3.8 +/- 0.5, respectively) compared to controls. CONCLUSIONS: EGF exerts a regulatory role on bicarbonate secretion by the pancreatic duct epithelium, independent of its effect on CA activity. Its inhibition of stimulated bicarbonate secretion could play a protective role in the setting of pancreatic inflammation, where increased levels of EGF are associated with reduced pancreatic juice production.