Alimentary TractAdaptive cytoprotection mediated by prostaglandin I2 is attributable to sensitization of CGRP-containing sensory nerves☆,☆☆
Section snippets
Rats and prostanoid receptor–knockout mice
Male Sprague–Dawley strain rats (specific pathogen free; Japan SLC, Inc., Hamamatsu, Japan), weighing 300–400 g, were starved for 18 hours before experiments began, but had free access to water. The experiments were performed on animals anesthetized with urethane (0.875 g/kg, by intraperitoneal injection; Aldrich Chemical Co., Milwaukee, WI).22 In some experiments, we also used IP receptor–knockout mice (IP−/−, male, 8 weeks old) recently developed by us.26 The IP receptor is specific for PGI2.
Effect of preperfusion of 1 mol/L NaCl on ethanol-induced gastric mucosal lesion in anesthetized rats
Perfusion with 50% ethanol after the preperfusion of physiologic saline resulted in gastric mucosal lesions that affected 20% of the area of the glandular stomach (Figure 1A, open column).
Discussion
The major arachidonate metabolites in the stomach were reported to be PGI2 and PGE2.30, 36 It has also been reported that the mild irritants that induce cytoprotection, such as NaCl solution, NaOH solution, and sodium taurocholate, increased the endogenous PG formation in the stomach.5 There are suggestions that the cytoprotection by endogenous PGs is attributable to the increased mucosal blood flow.7 The simple idea was that PGI2 and PGE2 generated by mild irritant–dilated arterioles
Acknowledgements
The authors thank C. W. P. Reynolds for correction of the English of this manuscript.
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2016, Asian Pacific Journal of Tropical MedicineCitation Excerpt :Here, exposure of the gastric mucosa to luminal diluted ulcerogens or mild irritants will result in less damage following later exposure to strong necrotizing agents [62]. Several mechanisms have been postulated to account for adaptive cytoprotection including endogenous prostaglandin synthesis, stimulation of mucus or HCO3 secretion, mucosal vasodilation [63], and release of calcitonin gene-related peptide from the sensory nerves [64]. Cannabis or cannabinoid agonists, administered via systemic routes, however, were able to exert protective effect [25,41,43,44,46] making adaptive cytoprotection an unlikely mechanism.
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2013, European Journal of PharmacologyCitation Excerpt :This may be due to the dose of rebamipide used in current study; Mizoguchi et al. used rebamipide 100 mg/kg and observed a significant decrease in iNOS activity induced by indomethacin in the small intestinal mucosa of rats (Mizoguchi et al., 2001). PGE2 and PGI2 play an important role in protection (Boku et al., 2001; Konturek et al., 1982) and healing (Kobayashi et al., 1982) of stomach mucosa and renal homeostasis (Hao and Breyer, 2008); however these physiological effects can be compromised by PG inhibition. Particularly disturbing, profound renal vasoconstriction from PG inhibition carries severe ramifications, like increased stress pressure on glomeruli, tissue hypoperfusion, and ensuing renal damage (Murray and Brater, 1993; Risser et al., 2009).
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Address requests for reprints to: Masataka Majima, M.D., Ph.D., Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa, 228-8555, Japan. e-mail: [email protected]; fax: (81) 427-78-4467/8441.
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Supported by a grant from Academic Frontier Project of The Ministry of Education, Science, Sports, and Culture; a Parents' Association grant from Kitasato University School of Medicine; and a Kitasato University research grant.