sincalide and Gastritis

Gastrin/CCK-B receptors (CCKB-Rs) are present on parietal and enterochromaffin-like cells in the gastric mucosa but not on pit cells in the proliferative zone. Because serum gastrin levels are well correlated with the growth of the gastric pit, we examined whether pit precursor cells express CCKB-Rs using hypergastrinemic transgenic mice and a mouse pit precursor cell line, GSM06. In situ hybridization indicated that CCKB-R mRNA was limited to the lower one-third of the mucosa in control mice, whereas it was faintly distributed along the mid- to low glandular region in the hypergastrinemic transgenic mouse mucosa. CCKB-R-positive midglandular cells appear to have a pit cell lineage; therefore, GSM06 cells were used for an [(125)I]gastrin binding study. [(125)I]gastrin bound to the membrane fraction of the GSM06 cells when precultured with gastrin. Gastrin dose dependently induced CCKB-R expression in GSM06 cells and stimulated their growth. Thus these findings suggest that gastrin directly stimulates the growth of the pit cell lineage by inducing its own receptor in pit cell precursors.

Topics: Amino Acid Sequence; Animals; Cell Division; Gastric Mucosa; Gastrins; Gastritis; Gene Expression; Hypertrophy; In Situ Hybridization; Iodine Radioisotopes; Mice; Mice, Inbred ICR; Mice, Transgenic; Molecular Sequence Data; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sincalide; Stem Cells

The role of Helicobacter pylori infection in the control of lower esophageal sphincter (LES) motility, especially the occurrence of transient LES relaxations (TLESRs), was studied in eight H. pylori-positive and eight H. pylori-negative healthy subjects. During endoscopy, biopsy specimens were taken from the cardia, fundus, and antrum for determinations of H. pylori status, gastritis, and proinflammatory cytokine mucosal concentrations. LES motility was monitored during three different 30-min periods: baseline, gastric distension (barostat), and gastric distension with CCK infusion. Gastric distension significantly increased the TLESR rate, whereas CCK increased the rate of distension-induced TLESRs further and reduced resting LES pressure without significant differences between infected and noninfected subjects. H. pylori status did not influence resting LES pressure or gastric compliance. Cytokine mucosal concentrations were increased in infected patients, but no correlation was found with the TLESR rate, which was also independent of inflammation at the cardia, fundus, and antrum. These results suggest that H. pylori-associated inflammation does not affect the motor events involved in the pathogenesis of gastroesophageal reflux.

Topics: Adult; Compliance; Cytokines; Esophagogastric Junction; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Muscle Relaxation; Pain Threshold; Pressure; Sincalide; Stomach

Cholecystokinin (CCK) prevents macroscopic injury to the stomach from luminal irritants by an unknown mechanism. The present study was undertaken in conscious rats to ascertain what role gastric mucosal blood flow, sensory neurons, and endogenous somatostatin play in CCK-induced gastric protection. Subcutaneous administration of CCK (10-100 micrograms/kg) significantly reduced macroscopic injury to the acid-secreting portion of the stomach caused by 1 ml of orally administered acidified ethanol (150 mM HCl, 50% ethanol) and augmented gastric mucosal blood flow (fluorescent microspheres) in a dose-dependent fashion. However, although the protective response to CCK (100 micrograms/kg) was still present at 2 h, the blood flow response had returned to baseline by 45 min. Ablation of capsaicin-sensitive afferent neurons with capsaicin (125 mg/kg sc) did not negate CCK-induced protection. Pretreatment with exogenous somatostatin (1 pmol-1 nmol/kg sc) failed to prevent the damaging effects of acidified ethanol to gastric mucosa. Immunoneutralization of endogenous somatostatin with somatostatin monoclonal antibody (2 mg ip) did not reverse the protective actions of CCK. Thus the data suggest that although CCK may prepare the gastric mucosa to withstand a damaging insult by augmenting gastric mucosal blood flow, its protective mechanism is independent of intact sensory neurons and endogenous somatostatin.

Topics: Animals; Capsaicin; Cholecystokinin; Ethanol; Gastric Mucosa; Gastritis; Hydrogen-Ion Concentration; Neurotoxins; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Sincalide; Somatostatin; Time Factors