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Role of histamine H4 receptors in the gastrointestinal tract
No full textThe location and functional role of histamine H4 receptors (H4Rs) in the gastrointestinal tract (GI) is reviewed, with particular reference to their involvement in the regulation of gastric acid secretion, gastric mucosal defense, intestinal motility and secretion, visceral sensitivity, inflammation, immunity and carcinogenesis. H4Rs have been detected in different cell types of the gut, including immune cells, paracrine cells, endocrine cells and neurons; moreover, H4R expression was reported in human colorectal cancer specimens. Functional studies with selective H4R ligands demonstrated protective effects in several experimental models of gastric mucosal damage and intestinal inflammation, suggesting a potential therapeutic role of drugs targeting this new receptor subtype in GI disorders, such as allergic enteropathy, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and cancer
Measurement of gastric acid secretion in the anaesthetized rat
No full textThe protocols described in this unit are designed to assess the effects of substances on gastric acid secretion by the rat stomach, with the animal under general anesthesia. Both stimulatory and inhibitory effects of compounds can be evaluated and specific mechanisms of action can also be investigated. Acid secretion is induced by substances that directly activate parietal cell receptors (histamine and bethanechol), by indirect stimuli, like 2-deoxy-D-glucose, by electrical stimulation of vagal nerves, or by the peptide pentagastrin. Reference antisecretory drugs are represented by histamine H(2) receptor antagonists and proton pump inhibitors. This model allows the evaluation of complete dose-response curves together with a time-course of the secretory/antisecretory effects. Indirect effects involving activation or inhibition of vagal pathways are evaluated in intact animals by means of electrical vagal stimulation or in vagotomized animals
Cannabinoid CB1 receptors are involved in the regulation of rat gastric acid secretion
No full textThe effects of cannabinoid CB1 receptor activation (HU-210) and blockade (SR141716A) on gastric acid secretion were determined in anaesthetized rats with lumen perfused stomach. The selective CB1-receptor agonist HU-210 (0.01-0-1 mg kg−1, i.v.) did not affect basal acid secretion while causing inhibition (maximum reduction 74%) of the gastric acid secretion stimulated by pentagastrin (10μ kg−1, i.v.).
The inhibitory effect of HU-210 was reversed by the selective cannabinoid CB1-receptor antagonist SR141716A (1 mg kg−1, i.v.), but not by the selective CB2-receptor antagonist SR144528 (1 mg kg−1, i.v.).
These results suggest that cannabinoid CB1 receptors may mediate inhibitory effects on gastric acid secretion in the rat
Inhibitory effects of the beta3-adrenoceptor agonists SR58611A and BRL37344 on rat gastric acid secretion
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