Effects of the Anti-Gastric Secretory Drugs IT-066 and Omeprazole on Mitogenic Activities in the Gastric Juice of the Rat

Abstract

Background: Salivary epidermal growth factor (EGF) retains its biologic function in gastric juice and may play a physiologic role. Little is known, however, about the existence of mitogens other than EGF and the constitutional alterations of these factors in gastric juice by anti-secretagogues. Methods: The mitogenic activity was evaluated by measuring [³H]-thymidine incorporation, and the EGF contribution was determined by using a specific anti-rat EGF antibody. An H₂-receptor antagonist (IT-066) and a proton pump inhibitor (omeprazole) were used to determine whether these drugs alter the relative composition of active mitogens in gastric juice. Results: Normal gastric juice significantly increased DNA synthesis. This activity was suppressed by antibody (87–88%). Both drugs increased EGF concentrations and activity dose-dependently. IT-066 specifically increased total amount and activity of EGF. Approximately 50% of this activity was reduced by boiling or antibody. Conclusions: The major mitogenic activity of normal rat gastric juice depends on EGF, and anti-secretory drugs enhance the mitogenic activity by preserving and inducing intraluminal mitogens other than EGF.

Key Words:

• Epidermal growth factor
• gastric juice
• growth factor
• H₂-receptor antagonist
• mitogenic activity
• peptic ulcer
• proton pump inhibitor
• stomach