Search

Although hospitalizations and deaths attributable to peptic ulcer have decreased notably during the past decade, it is not certain whether this decrease is because of reduced incidence of new cases or changes in other factors, such as the severity of the disease. Several genetic traits associated with peptic ulcer have been recognized. Hyperpepsinogenemia I is the most prevalent. Peptic ulcer is a heterogeneous group of disorders with multiple genetic and environmental causes. One manifestation of the diversity of ulcer disease is the variety of physiologic abnormalities seen in patients. The use of endoscopy has enabled more reliable evaluation of new treatments. Histamine H2-receptor antagonists are the dominant mode of treatment, but increasing attention is being given to agents that enhance the resistance of the mucosa to injury, such as prostaglandins. Because of the lower frequency of side effects, proximal gastric vagotomy is gradually replacing truncal vagotomy with drainage. The possibility that endoscopic treatments, such as laser coagulation, may reduce mortality from bleeding ulcers is being investigated. [ABSTRACT FROM AUTHOR]

Both secretin, and the single substance which possesses both cholecystokinin and pancreozymin activity, have been shown to inhibit gastric acid secretory responses. Since potentiation may occur between pairs of stimulants of gastric secretion, the effects of combining secretin and cholecystokinin/pancreozymin have been studied in Heidenhain pouches stimulated by continuous intravenous pentagastrin. Evidence suggesting potentiation between these two inhibitor agents is presented. [ABSTRACT FROM PUBLISHER]

The effect of smoking three cigarettes over a one-hour period on the pentagastrinstimulated submaximal plateau of acid and pepsin secretion was observed in 12 healthy human volunteers comprising men and women and smokers and non-smokers. No significant overall change in secretion was observed. In one subject, however, acid secretion was significantly inhibited ( < 0·01) and in one individual significant late stimulation ( < 0·01) of both acid and pepsin was observed. [ABSTRACT FROM PUBLISHER]

The sulfated and unsulfated forms of cholecystokinin-octapeptide (CCK-8) were compared, with respect to their effect on gastric acid secretion, in the rat. Unsulfated CCK-8 stimulated acid secretion in a dose-dependent manner, while the sulfated form was without stimulatory effect; thus, sulfation of the tyrosine residue in the seventh position from the C terminus completely abolished the gastrin-like action of CCK-8. Compared with pentagastrin and human gastrin II, unsulfated CCK-8 gave lower calculated maximal response. While sulfated CCK-8 given alone had no effect on acid secretion, it caused marked inhibition of the plateau response to submaximal pentagastrin. This inhibition was surmountable with higher doses of pentagastrin, suggesting a competitive type of inhibition. It is, therefore, concluded that lack of sulfation of the tyrosine residue in the seventh position does not exclude CCK-8 from occupying the gastrin receptor; but does prevent the hormone-receptor interaction that leads to the secretory response. These observations in the rat are different from those in the dog where desulfation of tyrosine renders the CCK analog, caerulein, ineffective in its ability to stimulate acid secretion., (Copyright 2000 Academic Press.)

We investigated the effects of the sensory neuropeptide substance P (SP) on amylase and fluid secretion in the isolated vascularly perfused rat pancreas. SP inhibited CCK-induced amylase release and secretin-induced juice flow via the pancreatic duct in a dose-related fashion. Threshold inhibition occurred following addition of 10(-10) M SP to the perfusate, and maximal inhibition was seen with 10(-8) M SP. The effects of SP were partially blocked by both the neurokinin-1 (NK1) and neurokinin-2 (NK2) receptor antagonists. Atropine and TTX blocked SP-induced effects on both amylase secretion (26 and 63% blockade, respectively) and pancreatic juice flow (21 and 79% blockade, respectively). Excitation of pancreatic sensory nerves using capsaicin (in the absence of SP) inhibited both amylase and pancreatic juice flow via activation of the NK1 receptor. We conclude that SP inhibits exocrine secretion via an indirect neural mechanism.

The vagus is a mixed nerve containing cholinerrgic and non-cholinergic neurons. Vagal fibers interact with peptidergic neurons of the enteric nervous system which stain immunohistochemically for cholecystokinin, vasoactive intestinal polypeptide, and gastrin releasing peptide. The contribution of these peptidergic neurons in the pancreatic response to vagal stimulation is unknown. We tested the effect of specific inhibitor of these stimulants against vagally mediated exocrine secretion in rats. The response to vagal stimulation was blocked significantly by each of the following: the ganglionic blocker hexamethonium (100% inhibition); the muscarinic, cholinergic blocker atropine (85% inhibition); the specific cholecystokinin-A receptor blocker (91% inhibition); and a vasoactive intestinal polypeptide polyclonal antibody (89% inhibition). This observation is consistent with the hypothesis that potentiating interactions among several agonists mediate the vagal response. Our study, however, dose not exclude acetylcholine as the final common mediator.

Although cholecystokinin is localized within neuronal fibres of the pancreas, a physiological role for intrapancreatic cholecystokinin has not been identified. The strategy of this study was to elicit pure vagal stimulation electrically, and to use specific receptor antagonists to identify the mediators of exocrine pancreatic secretion. We conclude that vagal stimulation of the rat pancreas involves ganglionic neurotransmission and release of acetylcholine and cholecystokinin from intrapancreatic, postganglionic fibres. To our knowledge, this is the first study to demonstrate a physiological role for intrapancreatic cholecystokinin.

In recent decades, isolation of the peptides secreted by gastrointestinal neuroendocrine tumors has greatly advanced our understanding of the pathophysiology of the syndromes resulting from over-production of these biologically active compounds. Early detection of these lesions permits localization and surgical extirpation prior to the development of mestastatic disease. In 1995, early detection of gastrointestinal neuroendocrine tumors hinges on an appropriate index of suspicion on the part of the primary care physician. The prompt recognition of the typical clinical constellations of symptoms associated with these tumors is essential to their timely diagnosis and management.

Epidermal growth factor (EGF) is mitogenic to gastric mucosal cells, protects against gastric mucosal injury induced by ulcerogenic agents, and stimulates cell migration in many systems. Restitution, the rapid re-establishment of mucosal integrity following damage, involves epithelial cell migration and can be monitored by measuring the transmucosal potential difference (PD) of tissue mounted in an Ussing chamber. The role of EGF in restitution is poorly characterized. To assess the effect of exogenous EGF on restitution, samples of rat gastric mucosa were mounted in an Ussing chamber with a solution of 10 nM EGF bathing either the mucosal or serosal surface. Matched control tissues from the same animals were untreated. Mucosal damage was induced by exposure of tissues to hyperosmolar sodium chloride. Restitution following injury was monitored by measuring the recovery of transmucosal PD, which reflects the degree of mucosal integrity. Undamaged mucosa maintained a PD of approximately -30 mV for several hours (mucosa negative with respect to serosa). Mucosal exposure to 1.2 M NaCl for 2 min reduced the PD to near 0 mV. Thereafter, the PD returned in approximately 60 min to plateau at a value representing maximal recovery. Tissues mucosally treated with 10 nM EGF recovered following damage to a maximum of 60.2 +/- 5.1% of pre-exposure PD, while matched controls recovered to only 46.2 +/- 5.8%, a significant difference. Tissues serosally treated with EGF recovered to 61.0 +/- 3.2% and matched controls recovered to 51.1 +/- 2.9%, also a significant difference. These results suggest that both serosally and mucosally applied EGF stimulates the restitution of rat gastric mucosa in vitro.