Local and global cytosolic Ca2+ oscillations in exocrine cells evoked by agonists and inositol trisphosphate

Neural emergency system in the stomach

Peptidergic sensory neurons in the control of vascular functions: mechanisms and significance in the cutaneous and splanchnic vascular beds.

In recent years, infection of the stomach with the organism Helicobacter Pylori has been found to be the main cause of gastric ulcers, one of the common ailments afflicting humans. Excessive acid secretion in the stomach, reduction in gastric mucosal blood flow, constant intake of non-steroid anti-inflammatory drugs (NSAIDS), ethanol, smoking, stress etc. are also considered responsible for ulcer formation. The prevalent notion among sections of population in this country and perhaps in others is that "red pepper" popularly known as "Chilli," a common spice consumed in excessive amounts leads to "gastric ulcers" in view of its irritant and likely acid secreting nature. Persons with ulcers are advised either to limit or avoid its use. However, investigations carried out in recent years have revealed that chilli or its active principle "capsaicin" is not the cause for ulcer formation but a "benefactor." Capsaicin does not stimulate but inhibits acid secretion, stimulates alkali, mucus secretions and particularly gastric mucosal blood flow which help in prevention and healing of ulcers. Capsaicin acts by stimulating afferent neurons in the stomach and signals for protection against injury causing agents. Epidemiologic surveys in Singapore have shown that gastric ulcers are three times more common in the "Chinese" than among Malaysians and Indians who are in the habit of consuming more chillis. Ulcers are common among people who are in the habit of taking NSAIDS and are infected with the organism "Helicobacter Pylori," responsible for excessive acid secretion and erosion of the mucosal layer. Eradication of the bacteria by antibiotic treatment and avoiding the NSAIDS eliminates ulcers and restores normal acid secretion.

Capsaicin and Gastric Ulcers

Cholecystokinin (CCK) is an important physiologic mediator that regulates satiety and gastric emptying. We demonstrated previously that soybean peptone acts directly on rat small intestinal mucosal cells to stimulate CCK release. In the present study, we examined the effects of beta-conglycinin, a major component of soy protein, and its peptone on food intake and gastric emptying after an intraduodenal infusion of beta-conglycinin peptone in relation to CCK release and interaction with the mucosal cell membrane. Intraduodenal infusion of beta-conglycinin peptone inhibited food intake in a dose-dependent manner, but that of whole soy peptone or camostat did not. The suppression of food intake by beta-conglycinin peptone was abolished by an intravenous injection of devazepide, a selective peripheral CCK receptor antagonist. The beta-conglycinin peptone infusion strongly suppressed gastric emptying with marked increases in portal CCK levels. We also observed that the beta-conglycinin peptone dose dependently and more potently stimulated CCK release from isolated dispersed mucosal cells of the rat jejunum than did beta-conglycinin itself. This stimulation corresponded to the binding activity of the peptide or protein to solubilized components of the rat jejunum membrane as evaluated by surface plasmon biosensor. These results indicate that beta-conglycinin peptone suppresses food intake, and this effect may be due to beta-conglycinin peptone in the lumen stimulating endogenous CCK release with direct acceptance to the intestinal cells.

/pdf/soybean-b-conglycinin-peptone-suppresses-food-intake-and-1dbooo4dq6.pdf

Soybean β-Conglycinin Peptone Suppresses Food Intake and Gastric Emptying by Increasing Plasma Cholecystokinin Levels in Rats

The presence of circulating antibodies to calcitonin gene-related peptide (CGRP) enhanced the damaging effect of ethanol on the rat gastric mucosa. Taken together with previous experimental and morphological data the results suggest that CGRP released from the peripheral terminals of visceral afferent fibres plays a role in mediating gastric mucosal defence mechanisms.

The role of calcitonin gene‐related peptide in gastric mucosal protection in the rat

It is clear that the intestinal hormone cholecystokinin (CCK) inhibits gastric emptying, but doubts remain about the physiological significance of this action. Evaluation of the apparently conflicting data is complicated by the fact that little is known of the duration of action of CCK-releasing meals in delaying emptying. We have studied this issue by following the emptying of the second of two successive liquid test meals instilled into the stomach in conscious gastric fistula rats. Prior administration of peptone, but not saline, delayed the emptying of subsequently administered saline and delayed still further the emptying of subsequently administered peptone. The action of isotonic peptone lasted about 10 min from the initial instillation into the stomach. Radioimmunoassay of plasma CCK indicated a significant increase 5 min after intragastric peptone, and a still further rise occurred 5 min after administration of the second of two consecutive peptone meals; 21 min after the first meal, plasma CCK had returned to basal levels. Intravenous infusion of CCK in a dose that matched the inhibition of gastric emptying caused by peptone gave plasma concentrations about 35% higher than those seen 5 min after the second of two consecutive peptone meals. It is concluded that a liquid test meal of peptone delays gastric emptying in part through release of CCK and that the response lasts 10 min or less. The relatively short duration of action of endogenous CCK released by a single protein-rich meal in the rat should be kept in mind in interpreting the significance of studies on the physiology of CCK.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/expphysiol.1992.sp003635

The role of cholecystokinin in inhibition of gastric emptying by peptone in the rat.

Clostridioides difficile is a Gram-positive anaerobic bacterium that is the leading cause of hospital-acquired gastroenteritis in the US. In the gut milieu, C. difficile encounters microbiota-derived bile acids capable of inhibiting its growth, which are thought to be a mechanism of colonization resistance. While the levels of certain bile acids in the gut correlate with susceptibility to C. difficile infection, their molecular targets in C. difficile remain unknown. In this study, we sought to use chemical proteomics to identify bile acid-interacting proteins in C. difficile. Using photoaffinity bile acid probes and chemical proteomics, we identified a previously uncharacterized MerR family protein, CD3583 (now BapR), as a putative bile acid-sensing transcription regulator. Our data indicate that BapR binds and is stabilized by lithocholic acid (LCA) in C. difficile. Although loss of BapR did not affect C. difficile’s sensitivity to LCA, ΔbapR cells elongated more in the presence of LCA compared to wild-type cells. Transcriptomics revealed that BapR regulates the expression of the gene clusters mdeA-cd3573 and cd0618-cd0616, and cwpV, with the expression of the mdeA-cd3573 locus being specifically de-repressed in the presence of LCA in a BapR-dependent manner. Electrophoretic mobility shift assays revealed that BapR directly binds to the mdeA promoter region. Since mdeA is involved in amino acid-related sulfur metabolism and the mdeA-cd3573 locus encodes putative transporters, we propose that BapR senses a gastrointestinal tract-specific small molecule, LCA, as an environmental cue for metabolic adaptation.

/pdf/identification-of-a-bile-acid-binding-transcription-factor-23hfwffm.pdf

ER Forster

Papers

The role of calcitonin gene‐related peptide in gastric mucosal protection in the rat

The role of cholecystokinin in inhibition of gastric emptying by peptone in the rat.

Identification of a bile acid-binding transcription factor in Clostridioides difficile using chemical proteomics