Stimulation of gastroduodenal HCO3- secretion by lubiprostone mediated by different prostaglandin EP receptor subtypes

Авторы

  • Koji Takeuchi Kyoto Pharmaceutical University; Kyoto Research Center for Gastrointestinal Diseases
  • Shusaku Hayashi Kyoto Pharmaceutical University
  • Kikuko Amagase Kyoto Pharmaceutical University; Ritsumeikan University

DOI:

https://doi.org/10.33910/2687-1270-2020-1-2-92-100

Ключевые слова:

lubiprostone, HCO3- secretion, prostaglandin EP receptor subtypes, stomach, duodenum, rat

Аннотация

We examined the stimulatory effects of lubiprostone, a bicyclic fatty acid derived from prostaglandin E1 and a chloride channel type-2 opener (ClC-2), on HCO3- secretion in the rat stomach and duodenum, with a focus on the EP receptor subtypes involved in this action. Under urethane anesthesia, an ex-vivo chambered stomach or a duodenal loop was perfused with saline, and HCO3- secretion was measured at pH 7.0 using a pH stat-method. Lubiprostone (0.1–30 μM) was perfused in the chamber or loop for 10 min. Indomethacin, ONO-8711 (an EP1 antagonist), or AE5-599 (an EP3 antagonist) was given s.c. 1 h before the lubiprostone treatment, while AE3-208 (an EP4 antagonist) or CFTRinh-172 (a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor) was given i.p. 30 min before. Lubiprostone dose-dependently and significantly increased HCO3- secretion in both the stomach (≥ 10 μM) and duodenum (≥ 1 μM). The stimulatory effect in the stomach was significantly abrogated by a pretreatment with the EP1 antagonist, but not the EP3/EP4 antagonists or CFTR inhibitor, while that in the duodenum was significantly attenuated by the EP3/EP4 antagonists as well as the CFTR inhibitor. Indomethacin had no effect on the response of either tissue to lubiprostone. These results suggest that lubiprostone stimulated HCO3- secretion in the stomach and duodenum in a manner that was mediated by different EP receptor subtypes; the former was mediated by EP1 receptors, while the latter was mediated by both EP3 and EP4 receptors. CFTR/ClC-2 may be involved in the response observed in the duodenum, but not in the stomach.

Библиографические ссылки

Aihara, E., Nomura, Y., Sasaki, Y. et al. (2007) Involvement of prostaglandin E receptor EP3 subtype in duodenal bicarbonate secretion in rats. Life Sciences, vol. 80, no. 26, pp. 2446–2453. PMID: 17512019. DOI: 10.1016/j. lfs.2007.04.012 (In English)

Aoi, M., Aihara, E., Nakashima, M. et al. (2004) Participation of prostaglandin receptor EP4 subtype in duodenal bicarbonate secretion in rats. American Journal of Physiology: Gastrointestinal and Liver Physiology, vol. 287, no. 1, pp. G96–G103. PMID: 15194560. DOI: 10.1152/ajpgi.00038.2004 (In English)

Bao, H. F., Liu, L., Self, J. et al. (2008) A synthetic prostone activates apical chloride channels in A6 epithelial cells. American Journal of Physiology: Gastrointestinal and Liver Physiology, vol. 295, no. 2, pp. G234–G251. PMID: 18511742. DOI: 10.1152/ajpgi.00366.2007 (In English)

Bassil, A. K., Borman, R. A., Jarvie, E. M. et al. (2008) Activation of prostaglandin EP receptors by lubiprostone in rat and human stomach and colon. British Journal of Pharmacology, vol. 154, no. 1, pp. 126–135. PMID: 18332851. DOI: 10.1038/bjp.2008.84 (In English)

Cuppoletti, J., Malinowska, D. H., Tewari, K. P. et al. (2004) SPI-0211 activates T84 cell chloride transport and recombinant human ClC-2 chloride currents. American Journal of Physiology: Cell Psychology, vol. 287, no. 5, pp. C1173–C1183. PMID: 1521305. DOI: 10.1152/ajpcell.00528.2003 (In English)

Cuthbert, A. W. (2011) Lubiprostone targets prostanoid EP4 receptors in ovine airways. British Journal of Pharmacology, vol. 162, no. 2, pp. 508–520. PMID: 20883477. DOI: 10.1111/j.1476-5381.2010.01058.x (In English)

De Lisle, R. C., Mueller, R., Roach, E. (2010) Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype. BMC Gastroenterology, vol. 10, article 107. PMID: 20843337. DOI: 10.1186/1471-230X-10-107 (In English)

Flemström, G., Garner, A. (1982) Gastroduodenal transport: Characteristics and proposed role in acidity regulation and mucosal protection. American Journal of Physiology: Gastrointestinal and Liver Physiology, vol. 242, no. 3, pp. G183–G193. PMID: 7039351. DOI: 10.1152/ajpgi.1982.242.3.G183 (In English)

Flemström, G., Mattsson, H. (1986) Effects of omeprazole on gastric and duodenal bicarbonate secretion. Scandinavian Journal of Gastroenterology, vol. 21, suppl. 118, pp. 65–67. DOI: 10.3109/00365528609090894 (In English)

Flemström, G., Turnberg, L. A. (1984) Gastroduodenal defense mechanisms. Journal of Clinical Gastroenterology, vol. 13, no. 2, pp. 327–354. PMID: 6378442 (In English)

Hatazawa, R., Ohno, R., Tanigami, M. et al. (2006) Roles of endogenous prostaglandins and cyclooxygenase isozymes in healing of indomethacin-induced small intestinal lesions in rats. Journal of Pharmacology and Experimental Therapeutics, vol. 318, no. 2, pp. 691–699. DOI: 10.1124/jpet.106.103994 (In English)

Hayashi, S., Kurata, N., Yamaguchi, A. et al. (2014) Lubiprostone prevents nonsteroidal anti-inflammatory drug-induced small intestinal damage by suppressing the expression of inflammatory mediators via EP4 receptors. Journal of Pharmacology and Experimental Therapeutics, vol. 349, no. 3, pp. 470–479. DOI: 10.1124/jpet.114.213991 (In English)

Heylings, J. R., Garner, A., Flemström, G. (1984) Regulation of gastroduodenal transport by luminal acid in the frog in vitro. American Journal of Physiology: Gastrointestinal and Liver Physiology, vol. 246, no. 3, pp. G235– G242. DOI: 10.1152/ajpgi.1984.246.3.G235 (In English)

Hogan, D. L., Yao, B., Steinbach, J. H., Isenberg, J. I. (1993) The enteric nervous system modulates mammalian duodenal mucosal bicarbonate secretion. Gastroenterology, vol. 105, no. 2, pp. 410–417. PMID: 8335196. DOI: 10.1016/0016-5085(93)90714-n (In English)

Koyama, M., Hayashi, S., Takahashi, K., Takeuchi, K. (2010) Lubiprostone stimulates HCO3- secretion in isolated mouse stomachs in vitro through activation of prostaglandin EP1 receptors. Gastroenterology, vol. 138, no. 5, suppl. 1, p. S-59. DOI: 10.1016/S0016-5085(10)60269-7 (In English)

Kunikata, T., Tanaka, A., Miyazawa, T. et al. (2002) 16,16-Dimethyl prostaglandin E2 inhibits indomethacin-induced small intestinal lesions through EP3 and EP4 receptors. Digestive Diseases and Sciences, vol. 47, no. 4, pp. 894–904. PMID: 11991626. DOI: 10.1023/a:1014725024519 (In English)

Li, C., Naren, A. P. (2005) Macromolecular complexes of cystic fibrosis transmembrane conductance regulator and its interacting partners. Pharmacology & Therapeutics, vol. 108, no. 2, pp. 208–223. PMID: 15936089. DOI: 10.1016/j.pharmthera.2005.04.004 (In English)

Mizumori, M., Akiba, Y., Kaunitz, J. D. (2009) Lubiprostone stimulates duodenal bicarbonate secretion in rats. Digestive Diseases and Sciences, vol. 54, no. 10, pp. 2063–2069. PMID: 19657734. DOI: 10.1007/s10620-009- 0907-0 (In English)

Norimatsu, Y., Moran, A. R., MacDonald, K. D. (2012) Lubiprostone activates CFTR, but not ClC-2, via the prostaglandin receptor (EP4). Biochemical and Biophysical Research Communications, vol. 426, no. 3, pp. 374–379. PMID: 22960173. DOI: 10.1016/j.bbrc.2012.08.097 (In English)

Regan, J. W. (2003) EP2 and EP4 prostanoid receptor signaling. Life Sciences, vol. 74, no. 2–3, pp. 143–153. PMID: 14607241. DOI: 10.1016/j.lfs.2003.09.031 (In English)

Schey, R., Rao, S. S. (2011) Lubiprostone for the treatment of adults with constipation and irritable bowel syndrome. Digestive Diseases and Sciences, vol. 56, no. 6, pp. 1619–1625. PMID: 21523369. DOI: 10.1007/s10620-011- 1702-2 (In English)

Schiffhauer, E. S., Vij, N., Kovbasnjuk, O. et al. (2013) Dual activation of CFTR and CLCN2 by lubiprostone in murine nasal epithelia. American Journal of Physiology: Lung Cellular and Molecular Physiology, vol. 304, no. 5, pp. L324–331. PMID: 23316067. DOI: 10.1152/ajplung.00277.2012 (In English)

Schwiebert, E. M., Cid-Soto, L. P., Stafford, D. et al. (1998) Analysis of ClC-2 channels as an alternative pathway for chloride conduction in cystic fibrosis airway cells. Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 7, pp. 3879–3884. DOI: 10.1073/pnas.95.7.3879 (In English)

Sugamoto, S., Kawauchi, S., Furukawa, O. et al. (2001) Role of endogenous nitric oxide and prostaglandin in duodenal bicarbonate response induced by mucosal acidification in rats. Digestive Diseases and Sciences, vol. 46, no. 6, pp. 1208–1216. PMID: 11414296. DOI: 10.1023/a:1010603026913 (In English)

Takeuchi, K. (2014) Prophylactic effects of prostaglandin E2 on NSAID-induced enteropathy — role of EP4 receptors in its protective and healing-promoting effects. Current Opinion in Pharmacology, vol. 19, pp. 38–45. PMID: 25063918. DOI: 10.1016/j.coph.2014.07.005 (In English)

Takeuchi, K., Furukawa, O., Okada, M. et al. (1990) Influence of stress on gastric alkaline secretion in rats. Journal of Pharmacology and Experimental Therapeutics, vol. 252, no. 3, pp. 1228–1233. PMID: 2319469. (In English)

Takeuchi, K., Furukawa, O., Tanaka, H., Okabe, S. (1986) A new model of duodenal ulcers induced in rats by indomethacin plus histamine. Gastroenterology, vol. 90, no. 3, pp. 636–645. PMID: 3943695. DOI: 10.1016/0016- 5085(86)91118-2 (In English)

Takeuchi, K., Kita, K., Hayashi, S. Aihara, E. (2011) Regulatory mechanism of duodenal bicarbonate secretion: Roles of endogenous prostaglandins and nitric oxide. Pharmacology & Therapeutics, vol. 130, no. 1, pp. 59–70. PMID: 21185865. DOI: 10.1016/j.pharmthera.2010.12.006 (In English)

Takeuchi, K., Matsumoto, J., Ueshima, K., Okabe, S. (1991) Role of capsaicin-sensitive afferent neurons in alkaline secretory response to luminal acid in the rat duodenum. Gastroenterology, vol. 101, no. 4, pp. 954–961. PMID: 1889720. DOI: 10.1016/0016-5085(91)90721-v (In English)

Takeuchi, K., Ogawa, Y., Kagawa, S., Ukawa, H. (2002) Gastric ulcerogenic responses following barrier disruption in knockout mice lacking prostaglandin EP1 receptors. Alimentary Pharmacology & Therapeutics, vol. 16, suppl. 2, pp. 74–82. PMID: 11966527. DOI: 10.1046/j.1365-2036.16.s2.21.x (In English)

Takeuchi, K., Ukawa, H., Furukawa, O. et al. (1999) Prostaglandin E receptor subtypes involved in gastroduodenal bicarbonate secretion in rats and mice. Journal of Physiology and Pharmacology, vol. 50, no. 2, pp. 155–167. PMID: 10424714. (In English)

Takeuchi, K., Yagi, K., Kato, S., Ukawa, H. (1997) Roles of prostaglandin E-receptor subtypes in gastric and duodenal bicarbonate secretion in rats. Gastroenterology, vol. 113, no. 5, pp. 1553–1559. PMID: 9352857. DOI: 10.1053/gast.1997.v113.pm9352857 (In English)

Tuo, B.-G., Sellers, Z.M., Smith, A.J. et al. (2004) A role for CagA/VacA in Helicobacter pylori inhibition of murine duodenal mucosal bicarbonate secretion. Digestive Diseases and Sciences, vol. 49, no. 11–12, pp. 1845–1852. DOI: 10.1007/s10620-004-9582-3 (In English)

Tuo, B., Song, P., Wen, G. et al. (2009) Helicobacter pylori vacuolating cytotoxin inhibits duodenal bicarbonate secretion by a histamine-dependent mechanism in mice. The Journal of Infectious Diseases, vol. 199, no. 4, pp. 505–512. PMID: 19099486. DOI: 10.1086/596318 (In English)

Woodward, D.F., Jones, R.L., Narumiya, S. (2011) International union of basic and clinical pharmacology. LXXXIII: Classification of prostanoid receptors, updating 15 years of progress. Pharmacological Reviews, vol. 63, no. 3, pp. 471–538. PMID: 21752876. DOI: 10.1124/pr.110.003517 (In English)

Опубликован

05.06.2020

Выпуск

Раздел

Экспериментальные статьи