Prostaglandin E 2 aggravates gastric mucosal injury induced by histamine in rats through EP1 receptors

• Published in: Life sciences (1973) Vol. 74; no. 5; pp. 629 - 641
• Main Authors: Hase, Shoko, Yokota, Aya, Nakagiri, Akari, Takeuchi, Koji
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 19-12-2003
• Subjects: EP receptor subtype; Gastric injury microvascular permeability; Histamine; Prostaglandin E; Rat; EP receptor subtype; Histamine; Gastric injury microvascular permeability; Prostaglandin E; Rat
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2003.07.010

We demonstrated that prostaglandin (PG) E
2 aggravates gastric mucosal injury caused by histamine in rats, and investigated using various EP agonists which EP receptor subtype is involved in this phenomenon. Rats were used after 18 hr fasting. Histamine (80 mg/kg) dissolved in 10% gelatin, was given s.c., either alone or in combination with i.v. administration of PGE
2 or various EP agonists such as 17-phenyl PGE
2 (EP1), butaprost (EP2), sulprostone (EP1/EP3), ONO-NT012 (EP3) and ONO-AE1-329 (EP4). The animals were killed 4 hr later, and the mucosa was examined for lesions. The mucosal permeability was determined using Evans blue (1%). Histamine alone induced few lesions in the gastric mucosa within 4 hr. PGE
2 dose-dependently worsened the lesions induced by histamine, the response being inhibited by tripelennamine but not cimetidine. The effect of PGE
2 was mimicked by 17-phenyl PGE
2 and sulprostone, but not other EP agonists, including EP2, EP3, and EP3/EP4 agonists. The mucosal vascular permeability was slightly increased by histamine, and this response was markedly enhanced by co-administration of 17-phenyl PGE
2 as well as PGE
2. The mucosal ulcerogenic and vascular permeability responses induced by histamine plus PGE
2 were both suppressed by pretreatment with ONO-AE829, the EP1 antagonist. These results suggest that PGE
2 aggravates histamine-induced gastric mucosal injury in rats. This action of PGE
2 is mediated by EP1 receptors and functionally associated with potentiation of the increased vascular permeability caused by histamine through stimulation of H
1-receptors.