Role of salivary glands and epidermal growth factor (EGF) in gastric secretion and mucosal integrity in rats exposed to stress.
EGF, produced mainly by salivary glands, inhibits gastric acid secretion, stimulates the proliferation of gastric mucosal cells and protects the mucosa against various ulcerogens, but its role in the pathogenesis of stress ulcerations is unknown. In this study, rats with intact or resected salivary glands were exposed to water immersion and restraint stress (WRS) without and with pretreatment with exogenous EGF or dimethyl PGE2 (dmPGE2) at doses which were shown previously to protect the mucosa against topical irritants. During 1.5-12 h of WRS, the formation of gastric ulcerations increased progressively with the duration of stress reaching peak after 6 h of stress and being significantly higher in rats with removed salivary glands than in intact animals. Gastric acid secretion and DNA synthesis in oxyntic mucosa declined with the duration of WRS, but after sialoadenectomy a significant increase in gastric acid secretion and a further decline in DNA synthesis were observed after WRS. EGF contents in the gastric lumen and the gastric mucosa were several times higher in rats subjected to stress than in control unstressed animals, indicating that stress causes an extensive release of EGF. Both exogenous EGF (17 nmol/kg/h) and dmPGE2 (143 nmol/kg) prevented, in part, the formation of gastric lesions, while inhibiting gastric acid secretion both in rats with intact or resected salivary glands. We conclude that water immersion and restraint stress is accompanied by an excessive release of EGF, which appears to attenuate gastric secretion, enhances the DNA synthesis and may limit the formation of stress-induced gastric ulcerations.
Konturek
S J
SJ
Institute of Physiology, Academy of Medicine, Kraków, Poland.
Brzozowski
T
T
Konturek
P K
PK
Majka
J
J
Dembiński
A
A
D000818:Animals; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012469:Salivary Glands / Q000502:physiology*; D013276:Stomach Ulcer / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D013312:Stress, Physiological; D014867:Water / Q000378:metabolism*
D014867:Water; D004815:Epidermal Growth Factor; D004247:DNA