Polyamines and epidermal growth factor in the recovery of gastric mucosa from stress-induced gastric lesions.

Abstract

Polyamines such as spermine or putrescine, resulting from increased activity of ornithine decarboxylase (ODC), are known for gastroprotective and mucosal growth-promoting effects. EGF exhibits similar effects, but little is known about the involvement of polyamines in acceleration of the healing of stress-induced gastric lesions by epidermal growth factor (EGF). In this study, rats with intact or suppressed ODC activity by alpha-difluoromethy-ornithine (DFMO, 400 mg/kg i.p.) were subjected to 3.5 h of water immersion and restraint stress (WRS) without or with addition of spermine or EGF. At 0, 2, 6, 12, or 24 h after stress, rats were sacrificed. The number of gastric lesions was determined and gastric blood flow (GBF) was recorded by the H2 gas clearance technique. Stress produced gastric lesions (mean number 18+/-2 per stomach) and decreased GBF (by approximately 43%), but at 2, 6, 12, and 24 h after stress, these lesions and the decrease in GBF were gradually attenuated. Pretreatment with DFMO or removal of an endogenous source of EGF by salivectomy resulted in a marked decrease in mucosal DNA synthesis and significantly delayed the healing of stress lesions. EGF or spermine significantly accelerated ulcer healing and increased the GBF in rats with intact or removed salivary glands. DFMO significantly reduced the enhancement of healing and the increase in GBF induced by EGF, but failed to influence those induced by exogenous spermine. We conclude that polyamines play an important role in mucosal recovery from stress lesions due to acceleration of mucosal repair and increase in gastric microcirculation and that increased ODC activity and resulting excessive polyamine release appear to act as primary mediators of EGF-induced acceleration of the healing of stress lesions.