The effect of tegaserod on esophageal submucosal glands bicarbonate and mucin secretion.

Tegaserod, a 5-HT4 partial agonist, was shown to reduce esophageal acid exposure in patients with gastroesophageal reflux disease; however, its mechanism of action is poorly understood. Therefore, we have examined the effect of tegaserod on luminal bicarbonate and mucin secretion in the isolated perfused pig esophagus. We also studied its role in esophageal protection using SMG-bearing pig esophagus in comparison to the rabbit esophagus, which is devoid of them. The tissues were mounted in Ussing chambers, and acid injury was replicated by exposing the lumen to acid (pH 1.6) or acid/pepsin (pH 2.5). In pig esophagus, tegaserod increased bicarbonate secretion, but had no effect on basal mucin secretion. In Ussing chambers, tegaserod reduced injury to pig, but not rabbit esophagus exposed to acid (pH 2.5) plus pepsin. These results indicate that tegaserod stimulates SMG bicarbonate secretion, an effect that likely accounts for the observed protection against acid-pepsin injury to pig, but not rabbit, esophagus.

Detection of change in threat-related and innocuous scenes among snake-fearful and snake-tolerant participants: data from the flicker task.

Visual change detection mirrors conscious attention. In the flicker task, pairs of scenes are presented rapidly; the second scene differs from the first, and the participant identifies the change. Change occurs in either a central-interest region or marginal-interest region of the scene. Detecting change in a marginal-interest region requires that attention be disengaged from the central-interest region. In two flicker experiments the dependent variable was the number of scene-pair repetitions before the change was identified. The independent variables were snake-fearful versus snake-tolerant participants, presence versus absence of a snake in the scene, and a change within a central-interest versus marginal-interest region. Snake-fearful participants took longer than snake-tolerant participants to identify changes in scenes without a snake. The explanation is offered that snake-fearful participants took longer than snake-tolerant participants to disengage attention from scenes in which a snake was present; delayed disengagement from scenes that included a snake impeded the detection of change in scenes that did not.

Characterization of esophageal submucosal glands in pig tissue and cultures.

The submucosal glands (SMGs) of the pig esophagus, like the human, secrete mucin and bicarbonate, which help in luminal acid clearance and epithelial protection. The aim of this study was to characterize histochemically the esophageal SMGs and a primary culture obtained from these glands. Tissues and cultures were stained with hematoxylin and eosin, periodic acid Schiff, Alcian blue, lectins, or cytokeratins. In the perfused esophagus, addition of carbachol increased mucin secretion by approximately 2-fold. The results indicate that [1] a method for culturing SMG cells was developed; [2] conventional staining indicates the presence of sulfated, acidic, and neutral mucopolysaccharides in glands and cultures; [3] lectin binding indicates the presence of N-acetyl glucosamine, N-acetyl neuraminic acid, N-acetyl galactosamine, and alpha-L: -fucose in mucous cells and cultures; [4] cytokeratin and lectin staining indicated similarities with Barrett epithelium (columnar metaplasia of the esophagus); and [5] cholinergic agonists enhance mucin secretion and this could play a significant role in esophageal protection.

HCO3- secretion in the esophageal submucosal glands.

The mammalian esophagus has the capacity to secrete a HCO(3)(-) and mucin-rich fluid in the esophageal lumen. These secretions originate from the submucosal glands (SMG) and can contribute to esophageal protection against refluxed gastric acid. The cellular mechanisms by which glandular cells achieve these secretions are largely unknown. To study this phenomenon, we used the pH-stat technique to measure luminal alkali secretion in an isolated, perfused pig esophagus preparation. Immunohistochemistry was used to localize receptors and transporters involved in HCO(3)(-) transport. The SMG-bearing esophagus was found to have significant basal alkali secretion, predominantly HCO(3)(-), which averaged 0.21 +/- 0.04 microeq.h(-1).cm(-2). This basal secretion was doubled when stimulated by carbachol but abolished by HCO(3)(-) or Cl(-) removal. Basal- and carbachol-stimulated secretions were also blocked by serosal application of atropine, pirenzipine, DIDS, methazolamide, and ethoxzolamide. The membrane-impermeable carbonic anhydrase inhibitor benzolamide, applied to the serosal bath, partially inhibited basal HCO(3)(-) secretion and blocked the stimulation by carbachol. Immunohistochemistry using antibodies to M(1) cholinergic receptor or carbonic anhydrase-II enzyme showed intense labeling of duct cells and serous demilunes but no labeling of mucous cells. Labeling with an antibody to Na(+)-(HCO(3)(-))(n) (rat kidney NBC) was positive in ducts and serous cells, whereas labeling for Cl(-)/HCO(3)(-) exchanger (AE2) was positive in duct cells but less pronounced in serous cells. These data indicate that duct cells and serous demilunes of SMG play a role in HCO(3)(-) secretion, a process that involves M(1) cholinergic receptor stimulation. HCO(3)(-) transport in these cells is dependent on cytosolic and serosal membrane-bound carbonic anhydrase. HCO(3)(-) secretion is also dependent on serosal Cl(-) and is mediated by DIDS-sensitive transporters, possibly NBC and AE2.