Can EP4 agonist alleviate gastric lesions?

Over 300 million patients use non-steroidal anti-inflammatory drugs (NSAIDs) in the world to treat pain, arthritis, fever and other diseases. Nearly 30% of the users suffer from gastric lesions and bleeding. To mitigate NSAIDs' adverse effects on the stomach, misoprostol, a non-selective prostaglandin E1 (PGE1) analogue, has been prescribed as the first choice for prevention of NSAID-induced injuries, but often induces severe adverse effects. There remain unmet medical needs for drugs with improved therapeutic profiles.

A research article published on November 7, 2009 in the World Journal of Gastroenterology addresses this question. A research team from United States investigated therapeutic potentials of a highly-selective EP4 agonist for treatment of a mouse gastric ulcer model in the presence or absence of indomethacin at various levels.

They found the EP4-selective agonist reduced high dose indomethacin-induced acute hemorrhagic damage and promoted mucous epithelial regeneration. Low-dose indomethacin aggravated ulcer bleeding and inflammation, and delayed the healing of the established chronic gastric ulcer. The EP4 agonist, when applied locally, not only offset indomethacin-induced gastric bleeding and inflammation, but also accelerated ulcer healing. In the absence of indomethacin, the EP4 agonist even accelerated chronic gastric ulcer healing and suppressed inflammatory cell infiltration in the granulation tissue. In vitro, the EP4 agonist protected human gastric mucous cells from indomethacin-induced apoptosis.

Their results suggest that EP4 agonists may mimic the gastric protective effects of PGE2 in the presence or absence of NSAIDs, and may show advantages over non-selective analogs such as misoprostol by minimizing adverse effects arising from activating all 4 subtype receptors of PGE2.

Reference: Jiang GL, Im WB, Donde Y, Wheeler LA. EP4 agonist alleviates indomethacin-induced gastric lesions and promotes chronic gastric ulcer healing. World J Gastroenterol 2009; 15(41): 5149-5156

http://www.wjgnet.com/1007-9327/15/5149.asp

Correspondence to: Guang-Liang Jiang, MD, PhD, Principal Scientist, Department of Biological Sciences, Herbert Research Center, Allergan, Inc., 2525 Dupont Dr., R&D-2B, Irvine, California, CA 92612, United States. jiang_guang-liang@allergan.com

Telephone: +1-714-2466794 Fax: +1-714-2462223

World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H. pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2008 IF: 2.081. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.