Overview of Acid Secretion

Here, we show that caffeine increased cAMP levels in HGT-1 cells, an effect that was inhibited by HED. HED itself reduced the cAMP level in HGT-1 cells, but did not affect proton secretion in HGT-1 cells. Therefore, it remains unclear whether or which signaling pathways are affected by HED.

Many of the inhibitory stimuli originate in the early small intestine (i.e. duodenum and jejunum) and act to inhibit secretion of stomach acid. They include both neural mechanisms as well as hormonal factors which are initiated by the presence of nutrients and acid-mediated irritation of the duodenal and jejunal small intestine mucosa. Important hormonal mediators are Gastrin Inhibitory Peptide and somatostatin. Advances in the understanding of physiologic control of gastric secretion raise the hope that an effective nonsurgical therapy for peptic ulcer disease will be developed soon.

In a previous study conducted by our research group [22], examination of the glandular epithelium of specimens of human oxyntic mucosa revealed that one particular type of cells contained NOS. These eNOS-immunoreactive cells, defined as endocrine cells, were in close contact with parietal cells. These two characteristics suggest that cells of this type release NO, which thus might be a paracrine regulator that directly affects the function of parietal cells.

The parietal cell basal membrane carries receptors for histamine (H 2 ), gastrin and acetylcholine. We used to believe that the gastrin and acetylcholine receptors on the parietal cell were particularly important in acid secretion. However, current evidence suggests that the gastrin receptors on the parietal cell are more concerned with cell growth than signalling for acid secretion.

If so, then the coupled activities of these transporters, with secondary coupling to the Na + ,K + -ATPase, may provide a mechanism (see Fig. 11) for the NaCl loading that is needed to generate the major electrochemical driving forces for gastric acid secretion. is unlikely to contribute to acid secretion in mouse (29) or volume regulation of stimulated parietal cells in the rabbit (28). Omeprazole was developed by a Swedish research group during a search for a drug that might inhibit the release of gastrin from the gastric mucosa. However, it soon became apparent that omeprazole was inhibiting the newly discovered acid pump on the surface membrane of the acid-secreting cell (Fig. 1).

Identification of the Influence of Bitter Taste on GAS in Vivo.

acid secretion in the stomach is controlled by
acid secretion in the stomach is controlled by

AG-1749 inhibited both the (H+ + K+)-adenosine triphosphatase activity in canine gastric microsomes and dibutyryl cyclic AMP-stimulated acid formation in isolated canine parietal cells and suppressed the acid secretion stimulated by histamine, pentagastrin, bethanechol or a peptone meal in Heidenhain pouch dogs; the ID50 values were between 0.2 and 0.7 mg/kg p.o. AG-1749 inhibited both the histamine-stimulated and the basal acid secretion in pylorusligated rats and prevented water immersion stress or aspirin-induced gastric lesions and mepirizole or cysteamine-induced duodenal ulcers in rats; the ID50 values were between 0.3 to 3.6 mg/kg p.o. or i.d.

Patients received either 1200 mg proglumide or 1200 mg cimetidine per day for 28 days. The results showed that both drugs significantly reduced clinical symptoms and gastric secretion. In patients treated with cimetidine there was a significant increase in blood gastrin levels and marked hypertrophy and hyperplasia of the antral mucosa was observed in almost all patients. No such changes were found in the patients treated with proglumide.

This paper reviews these advances with special emphasis upon those aspects of hormonal control, cyclic nucleotide function, and histamine activity which may have therapeutic applications. To confirm that caffeine induces GAS via gastric TAS2Rs, we demonstrated that the mRNA of 22 of 25 TAS2Rs as well as transducin is present in HGT-1 cells, and that the five TAS2Rs that can be activated by caffeine are present in the stomach mucosa.

OEC and LIM do not interfere with gastric H(+) secretion, serum gastrin or glutathione (GSH) level in gastric mucosa. But the gastroprotective action of OEC and LIM occurs due to an increase in the gastric mucus production induced by conserving the basal PGE(2) levels after challenge by agents harmful to the gastric mucosa. Given that LIM and OEC are excellent flavoring agents and also present gastroprotective actions, they can be regarded as a promising target for the development of a new drug for the prevention of gastric damage. Peptic ulcer (PU) is a disease of the gastrointestinal tract resulting from an imbalance between endogenous aggressive factors and defensive factors.

The secretion is inhibited by low pH. Gastrin is in the stomach and stimulates the gastric glands to secrete pepsinogen (an inactive form of the enzyme pepsin) and hydrochloric acid. The secretion of gastrin is stimulated by food arriving in the stomach.

The serum gastrin concentrations in the various experimental groups were measured 8-10 weeks after the operations. Elevated antral pH raised the serum gastrin concentration. The combination of elevated antral pH and the passage of food over the pyloric glands produced gastrin cell hyperplasia.

The numbers of antral gastrin cells were doubled and the numbers of antral somatostatin cells half that in the controls. These results show that long-standing lansoprazole-evoked hypergastrinemia affects the ECL cell similarly to omeprazole, ranitidine and other acid secretion inhibitors. To further understand the role of the peptide hormone gastrin in the development and function of the stomach, we have generated gastrin-deficient mice by gene targeting in embryonic stem cells. Mutant mice were viable and fertile, without obvious visible abnormalities.

Bitter tastants elicit bitterness through a family of oral taste type 2 bitter receptors (TAS2Rs) (11). Humans express approximately 25 TAS2 receptors, of which five TAS2Rs, TAS2Rs 7, 10, 14, 43, and 46, can be activated by caffeine (12). In addition to the mouth, TAS2Rs have also been identified in nongustatory tissues, including airway epithelia (13), brain (14), intestinal cells (15, 16), and the gastric epithelia of rats and mice (17, 18).

Acid formation in the glands was stimulated by histamine, dibutyryl cAMP (DBcAMP), and high extracellular K+ concentrations, and the glandular secretory response was measured by changes in oxygen consumption and in accumulation of the weak base [14C]aminopyrine (AP). The substituted benzimidazoles inhibited AP accumulation induced by all stimulants in a dose-dependent noncompetitive manner.

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