Modulatory Effect of Esophageal Intraluminal Mechanical and Chemical Stressors on Salivary Prostaglandin E2 in Humans

Abstract

As has been demonstrated, infusion of hydrochloric acid (HCl) and pepsin into the human esophageal lumen, which mimics the natural gastroesophageal reflux, results in a significant increase in salivary volume, salivary bicarbonate and epidermal growth factor. However, the impact of intraluminal acid/pepsin solution on salivary prostaglandin E2 (sPGE2), the major protective factor of the upper alimentary tract, has never been explored. Therefore, using the newly developed esophageal perfusion model, the impact of both mechanical and chemical stimuli of the esophagus on sPGE2 secretion in humans was studied. Salivary PGE2 was assessed in saliva collected during basal conditions, chewing of parafilm, placement of intraesophageal tubing, inflation of intraesophageal balloons, and perfusion with sodium chloride, HCl, or HCl/pepsin solutions. The concentration of sPGE2 was measured using the RIA kit from Amersham (Arlington Heights, IL) after the solid-phase extraction and derivatization. The concentration of sPGE2 in the basal saliva was (mean +/- standard error of mean) 186 +/- 31 pg/mL and was similar during the chewing of parafilm (171 +/- 32 pg/mL). The placement of intraesophageal tubing, however, resulted in a significant decline of sPGE2 concentration to the value of 91 +/- 22 pg/mL (P < 0.01). This decline was maintained when intraesophageal balloons, which compartmentalized a 7.5 cm perfused segment of the esophagus, were inflated (86 +/- 17 pg/mL; P < 0.01). This decline was potentiated further when subsequent perfusion with saline was implemented to reach the lowest value of 46 +/- 17 pg/mL (P < 0.001 versus basal and P < 0.05 versus tubing and balloon evoked values) at the end of the perfusing procedure. Esophageal perfusion with acid and acid/pepsin solution, however, partly restored the significant decline in sPGE2 concentration observed during prolonged perfusion with saline. The sPGE2 output during basal conditions was 89 +/- 13 pg/min and increased dramatically during stimulation by placement of intraesophageal tubing (241 +/- 48 pg/min; P < 0.01) and inflation of intraesophageal balloons (244 +/- 48 pg/min; P < 0.01). Subsequent esophageal perfusion with saline resulted in a gradual decline of sPGE2 output evoked by mechanical stimuli that reached the final value of 178 +/- 39, which was not significantly different from that observed in the basal condition (P < 0.1 versus basal value). Introduction of HCl and pepsin into the perfusing solution significantly prevented the decline of sPGE2 output observed during perfusion with saline (252 +/- 36 pg/min; P < 0.01 versus basal). The modulatory impact of mechanical and chemical stimulation on sPGE2, demonstrated for the first time in humans, may suggest the potential contribution of salivary prostanoids to the maintenance of the integrity of the esophageal mucosa.

How to Make a Barrett Esophagus: Pathophysiology of Columnar Metaplasia of the Esophagus

“…Esophageal mucosal exposure to HCl/pepsin leads to a significant increase in the rate of salivary PGE 2 secretion (20). Since luminal PGE 2 is able to enhance the physiological properties of the mucous layer, especially to retard H + ion diffusion, it could be of value in the pre-epithelial defense against GERD or in the healing of already injured mucosa (20).…”

Significant Increase of Esophageal Mucin Secretion in Patients with Reflux Esophagitis After Healing with Rabeprazole: Its Esophagoprotective Potential

“…Such a study, however, should be conducted in the future with simultaneous assessment of esophageal acid exposure time during 24-h pH monitoring. This insight could be of great pathogenetic value, as the integrity of the esophageal mucosa depends upon equilibrium between aggressive factors and protective mechanisms [1,5,11,12].…”

“…This mucus/buffer layer is continuously eroded by the luminal mechanical and chemical forces and restored by continuous secretion from esophageal submucosal mucous glands as well as freshly swallowed salivary secretions [3,[12][13][14][15]. Of note, as we have recently demonstrated for the first time in humans, protective factors elaborated by salivary and esophageal submucosal mucous glands, especially bicarbonate and nonbicarbonate buffers, epidermal growth factor (EGF), and transforming growth factor alpha (TGFa) are significantly augmented by stimulation of serotonin receptor 5HT 4 [16].…”

The modified glucose clearance test: a novel non‐invasive method for differentiating non‐erosive reflux disease and erosive oesophagitis

“…When the secretion of saliva decreases, the acid clearance function of the oesophagus also decreases. There are protective mechanisms against oesophageal mucosal injury, such as bicarbonate and noncarbonated buffers, mucin, epidermal growth factor, prostaglandin E2 and transforming growth factor‐α, which are secreted by the oesophageal submucosal glands and by major and minor salivary glands 7, 21–31 . Salivary bicarbonate plays a significant buffering role in protecting the oesophageal mucosa from refluxed gastric acid 32 .…”