Gastric and Duodenal Anti-ulcer Activity of SKF 38393, a Dopamine D1-Receptor Agonist in Rats

Abstract

The effect of SKF 38393 (1-phenyl-7,8-diol-2,3,4,5-tetrahydro-1H-3-benzazepine), a specific dopamine D1-receptor agonist, was studied on pylorus-ligation and water immersion plus restraint stress-induced gastric ulcers, and cysteamine-induced duodenal ulcers in rats. Repeated administration of SKF 38393 (5 and 10 mg kg-1, p.o.) for six days was found to be effective in the prevention of gastric ulceration induced by water immersion plus restraint stress in rats. In 19-h pylorus-ligated rats, repeated treatment with SKF 38393 showed a significant reduction in the number and severity of ulcers. SKF 38393 did not alter the total gastric-mucosal carbohydrates:protein ratio; however, the gastric content volume and the free and total acidity were significantly reduced. In cysteamine-induced duodenal ulcers, the treatment with SKF 38393 for 6 days prevented the duodenal lesions. Our data suggests the involvement of dopamine D1 receptors in the anti-ulcer activity of SKF 38393, which could be largely attributed to its anti-secretory effect. Its anti-ulcer activity against water immersion plus restraint, also points towards a central mode of action, but its failure to alter the carbohydrate:protein ratio rules out any protective effect through the strengthening of the gastric mucosal barrier.

Identification and regional distribution of the dopamine D1A receptor in the gastrointestinal tract

“…An additional action of D 1 -like receptors that can enhance the DA induced anti-ulcerogenic effect is their reduction of gastric secretion. Thus various groups have shown that D 1 -like receptor selective agonists reduce, whereas antagonists augment, gastric acid production (9,18). The experiments presented here clearly demonstrate D 1A receptor protein and mRNA in gastric glands throughout the fundus and body and pyloric regions of the stomach, providing strong evidence that this DA receptor subtype mediates, at least in part, these gastric actions.…”

Dopamine regulates colonic glial cell‐derived neurotrophic factor secretion through cholinergic dependent and independent pathways

“…D 1 receptor signalling negatively regulates neuroinflammation (Yan et al, 2015). Furthermore, a D 1 receptor agonist such as SKF38393 or fenoldopam is effective in reducing the duodenal lesions induced by cysteamine in rats, while a D 2 receptor antagonist such as sulpiride reduces ulcer formation (Desai et al, 1995(Desai et al, , 1999 Parmar, 1994). Our previous studies showed that D 1 and D 2 recpetors are widely present in the ENS of rat colon (Zhang et al, 2015).…”

Research progress on the roles of dopamine and dopamine receptors in digestive system diseases

“…Promotes gastric peristalsis and emptying, in addition to inhibiting reflux of gastric contents after meals; can increase pressure on the lower oesophageal sphincter [41,90,91] Sulpiride DRD2 inhibitor Can reduce the secretion of gastric protein and gastric acid and inhibit the development of gastric ulcers [18,35,42] Cisapride DRD2 antagonist Can increase the release of acetylcholine in the intestinal plexus to stimulate the movement of the lower oesophagus, stomach, and small intestine [19] SKF 38393 DRD1 inhibitor Inhibits the development of gastroduodenal ulcers [35] Metoclopramide DR antagonist Increases gastric emptying while also exerting antiemetic effects [39,40] Domperidone DRD2 antagonist Inhibits intestinal motility, regulates sodium absorption and mucosal blood flow, and has a protective effect against gastroduodenal ulcers [47,48] Calilazine DRD3 antagonist Can inhibit multiple drug resistance and make colon and lung cancer cells sensitive to antitumor drugs [52] Pimozite DRD2 antagonist Inhibits the growth and metastasis of colorectal cancer (CRC) [53] Thioridazine DRD2 antagonist Inhibits the growth of gastric cancer cells to exert antitumor effects; ameliorates hepatocellular carcinoma to possibly reduce the risk of tumour metastasis [54,83] Quinpirol DRD2 agonist Reduces the permeability of blood vessels and prevents excessive leakage of blood vessels, thereby decreasing the severity of UC [56,57,62] Bromocriptine…”