Antacid talcid activates in gastric mucosa genes encoding for EGF and its receptor. The molecular basis for its ulcer healing action.

Abstract

In previous studies [Gut 35 (1994) 896-904], we demonstrated that antacid talcid (TAL) accelerates gastric ulcer healing and provides better quality of mucosal restoration within the scar than the omeprazole (OME). However, the mechanisms of TAL-induced ulcer healing are not clear. Since growth factors promote cell proliferation, re-epithelization, angiogenesis and ulcer healing, we studied whether TAL and/or OME affect expression of epidermal growth factor (EGF) and its receptors (EGF-R) in both normal and ulcerated gastric mucosae. Rats with or without acetic acid-induced gastric ulcers (n = 64) received i.g. twice daily 1 mL of either: A) placebo (PLA); B) TAL 100 mg; or C) OME 50 mg x kg(-1) for 14 d. Studies of gastric specimens: 1) ulcer size; 2) quantitative histology; 3) expression of EGF mRNAs was determined by RT/PCR; 4) gastric sections were immunostained with antibodies against EGF and its receptors. In non-ulcerated gastric mucosa of placebo or omeprazole treated group, EGF expression was minimal, while EGF-R was localized to few cells in the mucosal proliferative zone. Gastric ulceration triggered overexpression of EGF and its receptor in epithelial cells of the ulcer margin and scar. In ulcerated gastric mucosa TAL treatment significantly enhanced (versus PLA and omeprazole) expression of EGF and EGF-R. OME treatment reduced expression of EGF in ulcerated mucosa by 55 +/- 2% (P < 0.01). It is concluded that: 1) treatment with TAL activates genes for EGF and its receptor in normal and ulcerated gastric mucosae; 2) since EGF promotes growth of epithelial cells and their proliferation and migration, the above actions of TAL provide the mechanism for its ulcer healing action and improved (versus OME) quality of mucosal restoration.

• Authors: A S Tarnawski, M Tomikawa, M Ohta, I J Sarfeh
• Journal: Journal of physiology, Paris (J Physiol Paris) 2000 Mar-Apr Vol. 94 Issue 2 Pg. 93-8 ISSN: 0928-4257 [Print] France
• PMID: 10791688 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antacids
• Anti-Ulcer Agents
• hydrotalcite
• Aluminum Hydroxide
• Epidermal Growth Factor
• ErbB Receptors
• Omeprazole
• Magnesium Hydroxide

Topics

• Aluminum Hydroxide (pharmacology)
• Animals
• Antacids (pharmacology)
• Anti-Ulcer Agents (pharmacology)
• Epidermal Growth Factor (biosynthesis, genetics)
• ErbB Receptors (biosynthesis, genetics)
• Fluorescent Antibody Technique, Direct
• Gastric Mucosa (metabolism)
• Gene Expression Regulation (drug effects)
• Immunohistochemistry
• Magnesium Hydroxide (pharmacology)
• Male
• Omeprazole (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction
• Stomach Ulcer (drug therapy, metabolism, pathology)