Stimulates gastric acid secretion

From a therapeutic point of view, selective agonists may become useful in the treatment of heart failure and catecholamine-insensitive cardiomyopathy, but only if compounds become available that do not stimulate gastric acid secretion or cause other unforeseen problems. 

Figure 3.1 A schematic representation of the control mechanism that stimulates gastric acid secretion, and the intervention points used to treat ulcers. The parietal cells and gastric cells form part of the epithelial cell lining of the stomach. Histamine release is usually triggered as part ofthe enteric nervous system response to distension of the stomach when food is eaten.

The principal xanthines of medical interest include caffeine, theophylline and aminophylline. Caffeine is synthesized by several plants and was originally isolated from tea in 1838. It is a methylxanthine (Figure 1.12) which stimulates the central nervous system, increasing mental alertness. It also acts as a diuretic and stimulates gastric acid secretion. It is absorbed upon oral administration and is frequently included in drugs containing an analgesic, such as aspirin or paracetamol. 

C. Histamine stimulates gastric acid secretion through an effect on Hj-receptors of gastric parietal cells. Although certain antihistamines are metabolized by cytochrome P450 enzymes, histamine does not induce their production. Histamine helps to maintain a wakeful state through an effect on Hj-receptors. Histamine-mediated hronchoconstriction is mediated by Hj-receptors, while histamine-mediated vasodilation occurs as a result of stimulation of Hi- and Hj-receptors. 

A. Gastrin, histamine, and acetylchohne stimulate gastric acid secretion. Pepsin is a digestive protein secreted by the stomach in response to a meal. Norepinephrine is a neurotransmitter that does not affect gastric acid secretion. 

On a weight basis 20 times more potent than cimetidine and 7.5 times more potent than ranitidine in inhibiting basal and pentagastrin stimulated gastric acid secretion. It is a competitive-noncompetitive inhibitor of receptors. It has a long-... 

Aihaara T et al Cholinergically stimulated gastric acid secretion is mediated by M3 and M5 but not Mi muscarinic acetylcholine receptors in mice. Am J Physiol 2005 288 G1199. 

Suppresses basal and stimulated gastric acid secretion by specific inhibition of the H /K ATPase enzyme system at the secretory surface of the gastric parietal cell... 

Actions At standard doses, both omeprazole and lansoprazole inhibit basal and stimulated gastric acid secretion more than 90%. Acid suppression begins within 1 to 2 hr after the first dose of lansoprazole, and slightly earlier with omeprazole. 

Inhibition of histamine-stimulated gastric acid secretion in the perfused stomach preparation in the anesthetized rat [9]. Compounds were administered intravenously. 

For testing the antisecretory potential gastric acid secretion is stimulated either by i.v. infusions of histamine (0.1 mg/kg/h), carbachol (10 ig/kg/h), or pentagastrin (8 rg/kg/h). When stimulated gastric acid secretion has reached a stable plateau (after 1.5 hours) the candidate compound is administered orally or by i.v. injection and secreted fluid is collected at 15 or 30 min intervals and analyzed for free HC1. 

There are a variety of peptide hormones acting in the gut the gastrins stimulate gastric acid secretion secretin and somatostatin inhibit the production of gastrins. Cholecystokinin and somatostatin can inhibit gastric acid secretion directly, and the former one causes the gall-bladder to contract and thus force bile into the duodenum. 

Gastrin stimulates gastric acid secretion but also has growth-promoting effects on various cell types. Gastrin shares GPCRs with CCK, namely the CCK- A and -B receptors. 

Gastrin CCK-B receptor 14- and 17-residue peptide amide with a Glu rich region Stimulate gastric acid secretion Solution-phase and solid-phase V -Fmoc chemistry... 

In contrast to the different types of receptor antagonists, omeprazole, the first HVK -ATPase inhibitor used clinically, causes a comparable inhibition of stimulated gastric acid secretion irrespective of the kind of stimulation Figure 4.3). Acid secretion can be induced in the rat perfused stomach-lumen model by an initial injection of isobutyl-methylxanthine (IBMX, a phosphodiesterase inhibitor) followed by an infusion of forskolin (direct stimulation of adenylate cyclase). This kind of stimulation represents an... 

Figure 4.2. Inhibitory profiles of different kind of antisecretory receptor antagonists on stimulated gastric acid secretion in rat perfused stomach-lumen. Desglugastrin represents a gastrin analogue. Values are means +/- S.E.M., n = 4-5 rats.

Human pharmacology parallels animal pharmacology, especially that of the dog, with respect to the effective dose-range and duration of action. Omeprazole causes dose-dependent inhibition of basal and stimulated gastric acid secretion and reduction of intragastric acidity in healthy volunteers after single administration [96-98] or repeated daily administrations [96]. This was also seen in patients with peptic ulcer disease [99-102]. The inhibitory effect after a single administration lasts 2-3 days [96]. 

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