Although various animal and clinical studies have demonstrated the significant effect of salivary epidermal growth factor (sEGF) on esophageal morphology and function, its secretory patterns still remain inadequately explored. Therefore, we have studied the impact of esophageal mechanical and chemical stimuli on sEGF in humans. sEGF was measured in saliva collected during basal conditions, chewing of parafilm, placement of esophageal tubing, inflation of intraesophageal balloons, and perfusion with NaCl, HCl, and HCl/pepsin solutions. The concentration of sEGF was measured with a radioimmunoassay kit from Amersham (Arlington Heights, IL). The concentration of sEGF in basal saliva was (mean +/- SEM) 2.08 +/- 0.22 ng/ml. Chewing the parafilm resulted in a significant decline of sEGF concentration to the value of 1.39 +/- 0.16 ng/ml (p < 0.0005). Similar decline in sEGF concentration also prevailed after placement of intraesophageal tubing (p < 0.03), and inflation of intraesophageal balloons (p < 0.01). This decline intensified significantly when prolonged esophageal perfusion with saline was implemented (p < 0.03 vs. tubing). Substitution of NaCl with HCl in the second and third perfusion periods prevented the decline in sEGF concentration, whereas HCl accompanied by pepsin enhanced sEGF concentration. The rate of sEGF output was 0.90 +/- 0.13 ng/min during basal conditions and increased significantly during parafilm chewing (1.53 +/- 0.25 ng/min; p < 0.05). However, sEGF secretion during both placement of esophageal tubing and inflation of balloons increased 4.1- and 4.9-fold, respectively (p < 0.002 and < 0.00005), over the basal value, and 2.4- and 2.9-fold, respectively, over the parafilm stimulated secretion. Subsequently, we observed a further significant decline of sEGF output (p < 0.05) which was sustained during perfusion of the esophagus with saline. Interestingly, esophageal perfusion with HCl prevented the decline of sEGF secretion observed during perfusion with saline. sEGF output during esophageal perfusion with HCl/pepsin exhibited a strong increase, reaching the value of 5.86 +/- 0.70 ng/ml. This value corresponds to a 58% increase over the secretory rate observed during mechanical stimulation by placement of esophageal tubing (3.71 +/- 0.47; p < 0.05). HCl/pepsin-induced potentiation of sEGF secretion was also highly significantly increased over both the value recorded during basal (p < 0.0005) and parafilm-stimulated (p < 0.002) conditions. Subsequent substitution of HCl/pepsin solution with a final saline perfusate still maintained enhanced sEGF output, compared with both basal (p < 0.02) and parafilm-stimulated conditions (p < 0.02).(ABSTRACT TRUNCATED AT 400 WORDS)