Prostaglandins: effects on the gastrointestinal tract

Several prostaglandins have been shown to exert five major gastrointestinal actions. Inhibition of gastric acid secretion, orally and parenterally. Antiulcer activity (they prevent gastric and duodenal ulcers produced experimentally in animals, and they accelerate the rate of healing of duodenal ulcers in humans). Cytoprotection for the stomach, the small and the large intestine. Cytoprotection is defined as the property of many prostaglandins to protect the mucosa of the stomach and intestine from becoming inflamed and necrotic when this mucosa is exposed to noxious agents. Cytoprotection is separate from, and unrelated to, inhibition of gastric secretion. In humans, certain prostaglandins of the E type given at very low doses prevent gastric bleeding produced by aspirin and indomethacin. Stimulation of intestinal secretion, through increase of cyclic AMP formation. Stimulation of smooth muscle contraction. Certain prostaglandins are likely to be beneficial in the treatment of gastric ulcers, stress ulcers, duodenal ulcers, and perhaps gastritis and certain forms of inflammatory bowel disease.     

Atropine-induced gastrointestinal cytoprotection dependences to the intact of vagal nerve against indomethacin-induced gastrointestinal mucosal and microvascular damage in rats

The non-steroidal antiinflammatory drugs, such as an indomethacin (IND), cause mucosal ulceration and increase the mucosal vascular permeability in the gastrointestinal (GI) tract. Some exogenous agents, e.g. the atropine, can protect the GI mucosa against these ulcerogenic effects. The gastrointestinal functions and mucosal protection, however, are regulated by the vagal nerve. The aims of this study was to examine the dependence of atropine-induced GI cytoprotection to the vagal innervation against the development of IND-caused ulcers and microvascular damage in the mucosa of stomach and small intestine in rats. METHODS: the observations were carried out on CFY-strain rats. The mucosal damage was produced by subcutaneous administration of IND in a 20 mg/kg dose 24 h prior to the killing of animals at the same time as the start of atropine-application, which was given in a small dose (0.1 mg/kg) every 5 h. The subdiaphragmatic bilateral surgical vagotomy was done 24 h before the experiment. The vascular permeability, indicated by the microvascular endothel damage, was measured by the appearance and concentration of intravenously administered Evans blue into the GI mucosa. The number and severity of mucosal lesions and the Evans blue content of mucosa were determined in the stomach and small intestine. RESULTS: (1) The IND caused mucosal ulcers and Evans blue extravasation into the mucosa of the stomach and small intestine. (2) The IND-induced mucosal ulceration and vascular permeability significantly decreased after atropine-administration in the same parts of GI tract. (3) The extent of cytoprotective effect of atropine against the IND was decreased after bilateral surgical vagotomy. CONCLUSIONS: (1) The IND causes microvascular endothel damage in the stomach and small intestinal. (2) The atropine has a cytoprotective effect in the stomach and small intestine against the aggressive effects of IND without decrease of gastric acid secretion. (3) The intact vagal nerve is necessary to the function of cytoprotective mechanisms of atropine against the IND.     

Tissue-level cytoprotection

In vitro and ex vivo tissue models provide a useful level of biological organization for cytoprotection studies positioned between cultured cells and intact animals. We have used 2 such models, primary tissue cultures of winter flounder renal secretory epithelium and ex vivo preparations of rat intestinal tissues, the latter to access the microcirculation of exposed mesentery tissues. Herein we discuss studies indicating that differentiated functions are altered in thermotolerant or cytoprotected tissues. These functions include transepithelial transport in renal epithelium and attachment and transmigration of leukocytes across vascular endothelium in response to mediators of inflammation. Evidence pointing to inflammation as a major venue for the heat shock response in vertebrates continues to mount. One such venue is wound healing. Heat shock proteins are induced early in wound responses, and some are released into the extracellular wound fluid where they appear to function as proinflammatory cytokines. However, within responding cells in the wound, heat shock proteins contribute to the acquisition of a state of cytoprotection that protects cells from the hostile environment of the wound, an environment created to destroy pathogens and essentially sterilize the wound. We propose that the cytoprotected state is an anti-inflammatory state that contributes to limiting the inflammatory response; that is, it serves as a brake on inflammation.     

1,6-二磷酸果糖与细胞保护

1,6-二磷酸果糖是细胞内糖代谢的中间产物,是能在分子水平上调节细胞代谢中若干酶活性,作为恢复和改善细胞代谢的药物,可通过多方面因素减轻细胞损伤,从而对细胞起保护作用。     

Prostaglandins and Glaucoma

Human aqueous humour was found to contain a substance which contracted the rat stomach strip. The mean activity was significantly higher in specimens from open angle glaucoma cases than in specimens from patients with cataract. The pharmacological and chromatographic properties of the active material were studied in aqueous humour obtained from cadavers; activity seemed to be due to prostaglandin E₁. These results suggest that prostaglandin E₁ may play some part in the aetiology of open angle glaucoma.     

Prostaglandins in human seminal plasma. Prostaglandins and related factors 46

This study on human seminal plasma sought after the compounds which either possess the dienone chromophore or can be converted into it by treatment with sodium hydroxide. In addition, this investigation led to the isolation of 8 more (PGs) prostaglandins which were present in higher concentrations than the previously recognized PGs. Samples of human seminal plasma were subjected to silicic acid chromatography, reversed phase partition chromatography, thin layer chromatography, and gas liquid chromatography which isolated those 8 PGs not previously recognized. 4 of these compounds, PGE1-217, PGE2-217, PGE1-278, and PGE2-278 were known from earlier studies but had not been isolated from natural sources. The other 4 were 19 hydroxy derivatives of the 4 abovementioned compounds. The concentrations of the previously recognized PGs were recently determined and it was found that the 19 hydroxy derivatives were present in concentrations 4 times higher than the PGE compounds.     

Prostaglandins and opioids.

In guinea-pig small intestine, rat brain in vitro and neuroblastomaXglioma hybrid cells, opioids specifically inhibit the action of E prostaglandins. In the whole rat, E prostaglandins, administered centrally, antagonize the antinociceptive action of morphine. E prostaglandins also antangonize the induction of opioid tolerant/dependence. In turn, tolerance/dependent preparations respond with added intensity to E prostaglandins. The antagonism between opioids and E prostaglandins does not occur at the opioid receptor; but, certainly in some preparations and probably in others, this antagonism occurs at the coupling or catalytic unit of a neuronal adenylate cyclase that opioids inhibit and E prostaglandins stimulate. The proposition that antagonism of E prostaglandin at appropriate neurons in the brain is part of the natural mechanism of opioid analgesia remains possible, but unproven, and is worth continued investigation.