Ghrelin, a novel
peptide expressed in the gastrointestinal tract, especially in the gastric mucosa, exerts several biological activities including the stimulation of appetite and food intake, the stimulation of intestinal motility and the release of
growth hormone. The aim of this study was to examine the expression of
ghrelin in gastric mucosa after its exposure to
ethanol and its effects on gastric lesions induced by
ethanol with and without pretreatment with
indomethacin. Acute gastric lesions were induced by intragastric administration of 75%
ethanol in rats pretreated with saline-vehicle or
ghrelin injected intraperitoneally (i.p.) without or with i.p. pretreatment with
indomethacin. At the end of experiments, the rats were anesthetized, the stomach was exposed to measure gastric blood flow (GBF), to determine the area of gastric lesions and to take biopsy samples from the oxyntic mucosa for determination of transcripts of
ghrelin,
tumor necrosis alpha (
TNF-alpha) and
transforming growth factor alpha (
TGFalpha) using RT-PCR and to assess the generation of
PGE(2) by RIA. Exposure of gastric mucosa to 75%
ethanol resulted in numerous mucosal lesions of an area of about 115 mm(2) and in the increase of mucosal expression of
TNF-alpha,
PGE(2),
TGFalpha and
ghrelin with concomitant decrease in GBF. Exogenous
ghrelin reduced dose-dependently acute gastric lesions with simultaneous attenuation of GBF and a decrease in the expression of
TNF-alpha but not
TGFalpha. Pretreatment with indometahcin, which suppressed the generation of
PGE(2) by about 85%, augmented
ethanol-induced gastric lesions and eliminated the
ghrelin-induced protection of mucosa against
ethanol. We conclude that
ghrelin, whose mucosal expression is enhanced after exposure to
ethanol, exhibits a strong gastroprotection, at least in part, due to its anti-inflammatory action mediated by
prostaglandins.